Mehmet: All right. So are we
ready to go? All right, so thank...
Thanks everyone for tuning in for this last
session of the STEM village virtual
symposium.
This is session eight and we have
wonderful talks lined up for you.
My name is Mehmet Kurt I'll be co-chairing
this session with Matthew Sinton who
is the founder of The STEM Village, pronouns he/him,
and our first talk/ dialogue
will be between Dr Lisa Graumlich - I hope I am not
butchering your last name
and Melissa Watkinson and
it will be on an international,
intergenerational, intersectional uh
dialogue.
So I'm very much looking forward to this
and it's a pleasure to have you both
here and
take it away when you're ready.
Lisa: Thank you so much and thank you to the organizers,
it's... it's amazing to be here with all of
you, I just wish I
could see all of you, but I can't.
My name is
Lisa Graumlich. I go... I have she/her pronouns. 
I am the Dean
of the college of the environment at the
University of Washington.
and I am a paleoclimatologist. I've been
somebody that has been
asking the question Is climate changing because of human activity? For about the
last 40 years and it's a pleasure
to be with my colleague Melissa
Watkinson.
Melisa: Hi Lisa. Thanks so much,  it's nice to see you.
Thanks also to the organizers for
letting me participate in this
discussion today.
My name is Melissa Watkinson, I use she/her pronouns.
I'm a citizen of the Chickasaw nation of Oklahoma,
which is a native american tribe, that
was forcibly removed from our original
territories
in what is now called Alabama and
Mississippi.
I'm joining the symposium today from
Bremerton, Washington,
which is the traditional homelands of
the Suqwamish and Duwamish peoples.
It has become a growing practice in the
United States to acknowledge the first
stewards of the lands and waters
of the place where we are standing and
calling in from.
I'm a social scientist and Diversity
Equity and Inclusion lead at
Washington Sea Grant which is an
organisation whose mission is to help
people and marine life thrive
by supplying research, technical
expertise and educational activities,
that support the responsible use and
conservation
of ocean and coastal ecosystems.
Washington Sea Grant is located in the
College of Environment at University of
Washington, which is where I've had the
pleasure
Dean Lisa Graumlich.
So thanks again for inviting me to
participate with you.
Lisa: So I thought I'd lead it off by just
saying
a little bit about one of the themes
that Melissa and I hope to bring forward,
both in our remarks and
potentially in some really interesting Q&A
-type dialogue
and one of those themes is to me what I
call "the gifts of being gay".
So imagine if you
will, like I'm the Dean. I'm like this senior person
in the college and the college has 200-some faculty and it actually has like
800 research professionals like Melissa and
2000 students and
you know, like yeah, I get to know you if
you have a big
problem, you know, but do I get to know
people just to get to know people? Not
very much.
So I was at a some kind of meeting
about marine conservation and there was
Melissa and she was saying really smart
things,
and she kind of looked interesting and this was like... Does your generation use the word 'gaydar?'
Melissa: Yes (she laughs)
Lisa: Of course! Okay. So like, I'm like
hmm she looks interesting and then I
like
get on social media and not in like an
obnoxious stalky way, but she's like hmm,
and sure enough she has this like lovely
partner and this and so
I became more bold and said... I think I
said "Melissa like
I want to do coffee", and so Melissa and I
started like taking walks and drinking
coffee
and sharing stories about our lives and
as Dean I do not get to do this,
and so the gift of my
friendship with Melissa is that I have
learned a lot
about what an early career person
with sort of some lovely and wonderful
and complex intersecting identities,
working in this incredibly important
area of marine conservation;
what her work and her life are like
and to be honest I wouldn't have... I
wouldn't have asked her out for coffee
if it was not for this mutual
recognition that we shared something in
our personal life that went
above and beyond science. So Melissa
thank you for your friendship yeah and... and I hope as we're
sort of gathering today that we sort of
think about despite some of the
trials and tribulations we have as queer
people in STEM,
there's these moments of recognition and
they can be
super rich.
So that's how we got here with Melissa
and I talking to you. 
Melissa: Yeah as you're talking it's just making me reflect on
kind of this idea of representation and
how important it is and I know
particularly for my generation and
because I think it's more possible, that
there is representation of different
identities within
STEM fields and other fields right,
that it's always something that we kind
of talk about and is important.
so I... so having seen you, yeah... you know
and some others within
our college being out and gay
and that representation was important
for my own growth and identity
within my career and just hearing you
speak
though it sounds like that same that...
same representation is important acro- 
you know...
from your generation
to mine as well, which is something I
hadn't really considered before.
Just in terms of being able to
continue to connect with those
identities that you share with... so I
appreciate you sharing that.
Lisa Yeah, absolutely. So Melissa
to start this dialogue,
although I actually know some of the
answer to this, but how and when
did you come out?
Melissa: Yeah, so my… my journey is as everyone's
journey is...is unique. I... I would say...
I came out... I started coming out to my
very close friends
and very close cousins. I'm starting
around the age of 18,
and I was coming out as bisexual at
that time
and I think at that point that was
really
all the extent of what I felt had felt
confident in
and... and believed in for myself. 
I grew up
in... in a family that was... attended a
evangelical church, that would often
make me oppress and suppress my own...
myself... in
terms of
my own identity as a queer person
and that, you know, led me to getting
married at a very young age,
to a man and...
you know, having this kind of idea of
what I... I thought society expected of me in my life. I... you know... was not on a path
of ... of science. I was not on a path
of academia, really I was on a track that
would kind of
fulfil what I thought... you know a
'good woman' was supposed to do in our society...
which was... you know... communicated
through me... to me, by the
church and likely through
media and other formats and
I... I somehow... I think just through the different networks I was building
and community I was building in Seattle
my
... my lens opened up a little bit more
and so
I'm grateful for that... the opportunity to open up a little bit to myself
to myself and then
more to others as well and so
I actually finally came out to my
family
about three years ago actually, so fairly
recently came out to my family...
you know, out... and out as gay, which was
a big milestone for myself,
for anybody right who's coming out...
out of... out of the closet,
because it's a-
It takes a lot of courage, you know to...
to be that person and so
around that same time was when I started
in my
current position and I think it was
you know acknowledging that there are
others in our...
in our STEM field and in
the areas with... where we work that can
help me to gain some confidence that
it's...
you know... you can be successful, you can be...
show up as to work as who you are
and be true yourself at the same
time so, yeah. Lisa
how about you? I know that... I know that
your... your journey came
a little bit before mine (!) and...(Lisa laughs) a little bit different
so how about you? 
What... what was... what was your
journey for coming out?
Lisa: Well... you know certainly some parallels with respect to
various versions...
of feeling like it wasn't okay
and I think those messages were...
actually not that it wasn't okay, that it
just wasn't talked about
and so I knew I had these sort of really
deep longings
and they weren't... you know... I don't even
think i knew what the word lesbian
was and.. and so looked to...
my mother was an english teacher so I
would like, look to literature
and yes you can find like these tragic
lesbian stories and everybody always
dies at the end and you know, wasn't like
oh this
doesn't look so great...
and I go to college and I was really
excited because i saw
on a bulletin board a flyer and it was a
lesbian support group
and there was sort of notion... like support
like...
you know, like we needed help. I thought
oh my god, you know, that's me, and I was at a relatively large
university and I went to the meeting and
there were three people there
you know, this is the 70's, where...
what can I say... sort of drugs and alcohol
you know it was all sort of cool
and it was the first time I saw people
that I really think these people
are probably like indulging too
much. So there were two people there, that
were really just kind of getting drunk
and the other person was trying to
figure out how to go straight and I
thought oh dear, this is kind of like the stories I
was reading in the books and so kind of
went away from there
and like you Melissa I got married I was
like okay... I can just like...
and I got married to this... he's actually
a wonderful man, but he was like
really heterosexual like... like... like... this
guy
like he's like heterosexual so that
means I'm heterosexual
and we moved to Madison, Wisconsin
and on the very first 24 hours
of me being the newlywed
I'm like in Madison and it's filled with
these gorgeous
gay women like publicly displaying
affection
and I'm like oh no... oh no
oh no... I just like got married and it was
the wrong
choice, so I found a way to exit out of
that,
but it took... it took years to come out to
my parents and it's just... you know... it's
sort of (she sighs)...
you know... there's... it's... it's a process
 that we all do so...
So part of
one of the things we've had
conversations about
Melissa, are sort of messages
that friends and family and
mentors and colleagues
give you about sort of your career
like here you are queer and what's gonna
happen... you know... like how are you gonna
navigate that identity and...
and you know... the incredibly important
work you're doing as a social
scientist in marine conservation how's
that going?
Melissa: Well I think.. I... you know... in term... in terms of the identity of queer... you know, I.. I...
I guess I've always been queer and I've
always been...
indigenous, you know, a term that just
kind of reflects my
native heritage and
the journey of kind of owning those
different identities
has been a little bit... a little bit
different but...
I but... I think you know... acknowledge...
acknowledge my own
and known about my own indigenous
heritage
prior to knowing about my queerness,
so... so... I've always just kind of... and
that's
that's just inherent in who I am and so I think..I
...you know... a lot of... a lot of those kinds
of challenging questions actually first
came up
around that part of my identity and my
background being a native person, because a lot
of my work is working
with tribes in Washington state
and on conservation-related
topics that are important to me only
because
some of the... my native family and...
and the way that I grew up culturally
was related to the health and well-being
of our marine ecosystems and so
of those kinds of questions and... and
conversations with
those who are close to me in terms of
my career were...
were more related to, you know, how
because it... it's... it's not just an academic
lens right
it's a... it's an emotional...
a mental ...state,
that also... that I also... but also
requires
someone who is you know... has these kinds
of different relationships with
the marine environment to be doing that
kind of conservation work,
in a place where most of the people in
the organization don't actually
share those identities with you,
and so
that came about this similarly as being
gay right and so
...or being queer
you know in the in the broader sense
just...
just that your… your own identities are
are different than others ...
and so i think you know in terms of the
career journey
it's most... it's the biggest outcome I
think has led to building my awareness
around what kinds of... gaps there
are in terms of equity and
inclusion
of different people and community
members and voices within the work that
we're doing
and I know Lisa that's some of the
conversations that we've also...
we've also shared... especially now
as... the environmental movement and
environmental field is growing and
conversations of diversity, equity and
inclusion.
I think that's really been… what's has
centered
those conversations in the career and
among my
my colleagues... and I think that
you know... that kind of... that... that's also a journey,
you know. I… before I came out and I was
starting...
my first... my first job in this field,
I wasn't out, but the
organization... you know was at those -
the pride parades and
being very visible and present
in those areas, and then when it came
to like conversations that I was a part
of around
pride or LGBT, my voice was
often kind of silenced ...because I
wasn't out and
...and I think for me that was a... you
know... a waking... a wake-up moment
for me now,
reflecting on that moment. That
there are probably others with... that
we're working with who... might not be out, right and how do we
make a voice for them
in these places too? Going from that
to where I am now
and having Lisa as a friend and mentor
and other... other super... you know... supervisors
and mentors within our college who
are out and... and provide that strong
representation ...
that's been a good progress in my
own career journey
Lisa: You know I'm sure everyone in this
Zoom live stream/ YouTube space
all has that memory of those moments
where
you're quiet and your voice isn't there
and just...
how... frustrating and...
really sort of devastating that is and
it
reminds me of a story that interestingly
it's a story that goes way back to the
1980s and that I
was reluctant to share until just a few
years ago
it's about that sort of voice so
it's about my first years in the 1980s
as
an assistant professor at the University
of Arizona
...and I was very excited that I was in
a... I was the first woman hired in a unit
and
you know was kind of digging in my
assistant professorship
and was really...
excited when a senior mentor like a Vice
Provost who was
a woman and a scientist kind of took me
under her wing and she wanted to mentor
me and
it was Arizona so we would go hiking and
we would talk and
she was very accomplished and I felt
very trusting of her
and on one of these hikes she like gets
really serious
and she says to me Lisa, it's okay to be
gay, just don't tell anyone and I was like
okay...
I think that was kind of positive
like it was okay to be gay
I'm not supposed to tell anybody and
okay and she's like a Vice Provost so I
need to take her seriously and so
for a couple years I like...
I did that thing of like okay... I'm just
not gonna tell anybody and I'm going to like say these like... really stupid things
like... what'd you do over the weekend oh
my friend and I... you know did whatever
you know like you're just kind of like
putting up all these barriers and then
kind of never really being present,
because you're scared you're gonna say
things. So the story gets better,
so this fancy Vice Provost woman
nominates me
for a super prestigious fellowship it
was
50 people from the entire country over
all aspects of science would get this
sort of opportunity for a three-year
leadership college.
It's really complicated, you know, you
write an essay and then
you make it to the next level and you
get to write more essays and you make it
to the next level and
it all kind of culminates in
there's a hundred of us that will be
interviewed for 50
positions and they fly us
into a fancy internat-
actually I think it was Houston and
we're staying in a super fancy hotel
and we're gonna have an hour with the
selection committee
and I get like a really beautiful
suit and I have my talking points and
I'm all ready to talk
about my vision you know it's about
climate change and the future... of the
future
I'm all ready and it's going
really well and they're like scribbling
down notes and they're nodding at me and
I'm like oh man this is going to be
great
and I met the last question and they say
to me "what is the hardest thing you've
ever done?"
and you know when I'm in a groove and I
immediately know the hardest thing I've
ever done
is to come out and all I can hear is
that vice provost
woman saying like don't tell anybody,
don't tell anybody, and I just completely
froze
and I'm sure I looked like I was gonna throw up.
I felt like I was gonna throw up. 
I felt like like the deer in the
headlights
and I just like... I'm just silent and I'm...
like I'm gonna say it... no I'm not gonna say it
I'm gonna say it... I'm gonna say it
and I didn't say it I... said like this
really stupid
thing like oh like getting atmospheric
scientists to talk to biologists... I mean
like... it was like the stupidest thing and
I also like clearly looked terrified
and I walked out of the room remember
it's this fancy hotel
you know the hotel elevators where
there's mirrors on three sides.
I get in to the hotel elevator by
myself
and all I see is me... like oh my God,
and there I am and I've just like lost it
you know I just like lost this chance,
because I
would not come out and I literally like
looked myself in the eye and I said
you are never doing that again
and I didn't and what was crazy
was in particular the next couple of
years... yeah I didn't get the fellowship, but the next
couple years,
just kind of unleashed this creative,
bold leadership that...
you know... kind of got me to be the Dean I
am today and
it was because and I... I really wish I
could have eye contact with all of you
out there.
it was because I had my whole self in my
science
I wasn't always putting these barriers
up and so
for those of you that are hesitant
and... and have gotten these messages from
powerful people like
don't come out... don't listen to them...
listen to Melissa and me because
it really is that bringing your whole
self
to your work... all of our identities from
Melissa
her incredibly important understanding
of knowledge of what it means to be
indigenous
in a time in which that traditional
knowledge has always been but even more
so is critical
all of that needs to be there so
that's my story. But you know what's...
what's even crazy is
you know those... those... that lingering
homophobia,
I did not tell that story for decades.
I was too scared to tell that story so
yeah...
Melissa: Thank you so much for sharing that's a
real... it's really powerful to hear
and to reflect on how
culture and society and even our the
work that we're doing has evolved
over these generations in this time and...
I'm reflecting, you know, I feel like... you
know we're speaking to a global
audience right now
and we are...
we're both living you know... living
around the Seattle area, which is
known to be kind of a progressive city...
in a state that's... that's...
probably you know passed same-sex
marriage before
most of the rest of the country...and well I guess even like... less than two
months ago I was in a... on another call
with
my Sea Grant colleagues across the
United States
and talking about this concept of kind
of being able to show up as your full
self to work...
and then one person anonymously chat... put
in the chat box
or the Q&A box saying you know but
I'm a lesbian and I actually can't be
out...
within my Sea Grant program because of
the state where my Sea Grant program is...
I can legally... still be fired...
for coming out... for being
who I am
and I think within two weeks actually
the Supreme Court
made a decision that overruled that,
so now you can't legally be fired from
your position in the United States
for being out...
but that doesn't... that... you know... that... that
was just a symbol for me to recognize
too that... that's just kind of what was
happening and maybe in our bubble... that... that I wasn't aware of in other
parts of the United States and
let alone to this global community that
we're talking to.
So there are certain... are these
factors that...you know that are
the differences of Lisa and my
experience might transcend to
those kinds of experiences across
different...
different nations around the world
where... where it may still not be safe
for people to be out or visibly
queer in public... and so those are
privileges that I often
recognize and reflect on...
and you know and I... and I'm
and I do want to you know participate in
these activities i suppose
in terms of wanting to... change that for
folks you know...I... I...
feel so fortunate to not have to be in
that situation...
and to feel welcomed and so I hope that...
you know
more of these kinds of conversations can
encourage
the continued progression of that
acceptance in our… in the world...
one of the things that you and I... you
know have been talking about are kind of
the... the ways that queerness intersect
with
different parts of who we are
and our different identities and
in some ways you know... you talked about
you know... we have these different
superpowers...
as being queer and some of these
other ways, that
they... these superpowers are strengthened
and how
in other ways that we show up in the
world... do you have
some... some superpowers that... you kind of are able to pull out... (Lisa laughs) and... and...
what kinds of other identities
...strengthen those superpowers for you?
Lisa: It's funny... well I'm going to start
with
once again, sort of going way back...
so besides when I was in graduate school
besides... being a graduate research
assistant, I would also be a bartender at
a lesbian bar
and... and... it's so funny because you guys
can't even...
I'm kind of tall... I'm actually not that
athletic
but because I was tall, I was the one
that was
in charge of escorting
cranky men out of the bar when they came
to sort of cause trouble and... and so
first of all i think that we end up
...in our lives
in the gay community... in the queer community...
we... we cope with situations
you know we... we learn to listen... we learn
to be
sensitive to social situations and
assessing is there danger, is there not
danger and how do we diffuse danger etc.
etc. and so there's this
whole social awareness
and at times needing to step in
and intervene ... that I think of
as you know one of sort of the powers
that... that we get and I just... I just laugh,
because you know what early on as an
assistant professor
they'd be like these classroom
management questions that like
my peers had and it's like... like, this is
nothing. You know these are well-behaved
19 year olds, you know, you have not
been trying to escort drunk, angry men
out of a gay bar before...
so anyway... so... so there's... I think
there's ways...
the richness of... sort of the lives that
we live
but more seriously... I...
we... we've had some talks about this
Melissa... I feel like there's always this
insider/outsider...
identity that we have so you know as...
as a privileged white person you know
i like participate in science
as a woman there's... there's issues but
then
you know being queer there's always a
little bit of like
ooh am I part of the gang or I'm not part of
the gang and there's been ways
in which the kind of social part of how
we do science together
as I had been shut out of it and...
so I just kind of started doing
more and more deeply interdisciplinary
work
and this kind of... you know... particularly
to you Melissa this is going to kind of
seem
dull, like why would you do this, but to
try to get
physical scientists, biological
scientists and
social scientists to work to understand
climate change on vulnerable communities
that was like a radical idea yeah and...
and I think my comfort about it had to
do with
bridging identities and and talking
across in this case academic cultures
and... and so it really... the kind of
leadership
that I was able to bring to my work
really had to do with a lot of skills I
had that were just
from kind of navigating multiple
identities
does any of that resonate with you
actually?
Melissa: So Lisa and I kind of talked a little
bit briefly ahead of time what…
what kinds of topics to go over and
I
...literally my notes are reflective of
what you were just saying
...in preparation and... and... you know we've used the word code
switching before
and... and that can come in multiple
different ways and this...
in this kind of professional setting I
can definitely... you know... I've heard some
people call it bridge spanning
and... and I do think that that's one of
the bigger strengths that...
that I have and I think that's
very true as a result of... building
you know having that inward... inside and
outside
...identity outside you know...
presence ...you're spent... you're...
you're spanning these boundaries
bringing in... you know...
building... helping to support
collaborations... connecting people
across different sides together... and
you know I am a social scientist working
on transbound
or transdiscipline projects right when
these larger collaborations
...and I think that you know that's
likely a skill set that comes
straight from...having to
identify how that happens in our... in our...
in our lives that we've built over time
...and yeah I guess I definitely have
resonated...
with that experience for sure.
I had it...
I had this... this thought but it just
escaped me so (she laughs)
maybe end it there but...
yeah that's definitely... definitely huge
I would say...
I would say in addition to... to that...
that superpower one of the other things
that i think has propelled me to be able
to do that...
is you know I... I said I had always
been
you know up until recent up until I came
out to my family I
I came out as bisexual to many folks
...to those that were closest to me... I
also have... I'm biracial and... and so there's
always
this kind of sense I mean this... this is just assuming... you know... assuming that
these things are on a binary...as we know that they're... as we know they're not
but...this kind of like being in the middle like do I belong on this side or
that side you know... having to kind of
essentially be
like who am I? I'm also a middle child so you know where... where do I belong...and
so... you know... once I kind of had found that
and my...
the career that the trajectory i'm in...
it made me really want to utilize that... that own...
finding in myself to be able to help to
bridge the... those things that were kind
of...
you know... on those binary sides
previously and helped to bridge those
together and so i think that's a part of
it
...that has shaped that perspective for
me as well.
Lisa: Melissa like our usual conversations we
could like go deep on all of these
things but
you know I think it... I think it helps
break down
those binaries which we know... you know in science
aren't certainly in science and in
a lot of the work that we're both
engaging with which is trying to
translate and
the... the work that we do into knowledge
intersecting the lives and livelihoods
of people
you know the binaries aren't
for most of the problems we work on they
don't fall into binaries.
So I'm watching my
my clock in my little corner... and I
that one of the questions... I think let's... let me say this is my last question to
you so that we have time to have
anyone who wants to share their
superpowers; but
Melissa I used to see you all the time
on campus and now I haven't seen you for
like six
months, and how are you taking care of
yourself
in the midst of the pandemic and all of
the
yeah rage that we're feeling
right now about what's going on in this
country in terms of police brutality
that
just is not ending. So how are you...
are you taking care of yourself?
Melissa: I'm
doing okay.
I'm... I'm leaning on those who
...bring me comfort and I... and then... you
know... and thinking about this kind of
conversation around a queer village I
think that
...my partner and I are fortunate we
moved
and we bought a house and moved... just
outside the city
about a year ago and we're fortunate to
kind of quickly identify some other
queer couples that live nearby and
brought them into our kind of
quarantined bubble so
we've been able to have you know
backyard barbecues and share cocktails
and laughs and
talk about what's going on in the world ...
and really like leaning on that... on that
queer village that we have
in... in our... in our little neighbourhood
here
has been really helpful...that and
adopting a new dog has been providing a
lot of emotional support
and cuddles that you know we... we don't
get to
find otherwise so yeah it's... it's been...
it's been hard and... and also she helps
to show what I'm grateful... you know what...
what we can be grateful for.  How about you? How are you and your family doing Lisa?
Lisa: Well we're doing okay. We're... we're
you know we're all... physically healthy
but
we're... we're stressed. I have a 17-year-old daughter going into senior year in
high school and this is not what she
anticipated and she's black
and she's... we are
so deep into thinking about
what Black Lives Matter and what it
means for an
...an interracial family you know... so
we're...
so a lot of that, but I am really grateful and the
reason I'm in this sort of funny hotel
is
[her partner] and I took her off to the mountains
to... just to get away for 24 hours
and smell pine trees and
walk through sage and so... and eat a lot
of really good food
That's... that's our love language
it's
food and more food.
Melissa: so... so there might be some berries out there
Lisa: thank you. oh yeah.
we got to get up to the berries thank
you we will do that and...
and think of you. So
we have... when... listen I talked about this
we had this fantasy that... oh my gosh
there's something in the chat... Matthew
and our...
our wonderful behind the scenes people
keeping us
organized. Do we have some comments or
questions or superpowers being shared?
Can you help us?
Mehmet: I... I don't see questions as of
now but I have a question actually if
you don't mind.
So... I'm in academia too, so I'm an
assistant professor in
an engineering department. So there's
something in academia right
that is the power structure and the
hierarchy
that makes it hard for LGBTQ people to
be visible really it is
like you and melissa said right it is
mostly self-suppression in a way because
of... I believe because of the
power structure in the hierarchy and I
think that's even harder for graduate
students
or international graduate students who
depend on the funding to stay in the
United States right,
and for assistant professors it is the
tenure structure. There's always a power
structure that kind of suppresses the
visibility
right? So what is our advice for
graduate students or international
graduate students who are struggling
with
those problems?
Lisa: Melissa did you want to go first?
Melissa: yeah, maybe
we... Lisa and I like will likely have a
very different perspective on this
where we... where we're from so I graduated...
I went and finished graduate school in
2015... and... I
I... so my... so in my experiences... I think
following that...are
are applicable to this question and that
you know ...
...the one thing that really
got me through... so much of my experiences was...
was finding one... one to two people who
shared in similar identities to me
whether it was a student...
another fellow... a colleague
who could... who i could take regular
coffee breaks with and have those
working lunches right, where you're kind
of
kind of...maybe... maybe all you... maybe all you do
give each other a hug and and listen to
each other kind of vent
for 20 minutes each. Just because you
need that space to
vocalize some of those hardships and
i think that's one way to really kind of
take care of yourself and your community
and and i think coming from my
perspective that
that's where a lot of that
that
self power that self control can really
kind of... be maintained and sustained... I know
Lisa probably has a perspective in terms
of like how those systems in place
...within our... within academia can shift
a little bit
to... be more open to allow
visibility of queer folks.
Lisa: yeah... first of all I want to just say
Mehmet, what you brought up is so real
and particularly
the vulnerability of our international
students
has always been high and it's just you
know with the pandemic and sort of rules
about visas and
and sort of in the united states the
sort of
political climate about you know what it
means to be
you know not from the US is just so
painful right now
so all of that is real. I completely
agree with Melissa is
finding your network of people that
even like across the room like you can
just like your eyes can meet
and you like know like okay this is
someone who's a fellow traveler or
ally and and just nurturing and
changing holding on to those people but
then the other piece
is trying to figure out where there
are allied movements
for dismantling power and privilege
within
your institutions whether they're
academic or not
and so right now United States of course
the Black Lives Matter movement is so
important and of course it's important
for the lives, welfare of
our black, indigenous, people of colour
students, staff and faculty.
But every time policies
are made more same it benefits
queer people and it benefits people with
different abilities and its benefits
people with
on the spectrum it benefits... it benefits
everyone and so
you know the degree to which we
show up
for supporting the struggles
of of others
i think is a this way we're kind of
paying it forward
and creating the alliances that will
help us make
lasting change
Melissa: yeah that's powerful.
Lisa: I... I believe... Sorry, I'm looking at the chat (she laughs) We need more...
Mehmet: I know... I know... and I think Matthew has a question right? Matthew: hi
actually it's my husband that has a
question so i'm...
Mehmet: okay awesome.
Matthew: I'll let him ask it
Juan: Hi I've been listening in the background
and it's just amazing...
and I think one word that you just said
resonated with me and it's the power of
invisibility
...and this sort of role play that we
have to
all kind of play when it comes down to
you know hiding what we are in order to
achieve a position or
something in academia and i'm getting
to that stage where i feel like
we need to have more active roles in
taking up space and so i'm curious to
see
from you guys what's your
...approach to… to taking up that space
when... when when you're openly gay
...in... in
where it's ...otherwise very rigid...
Very academic...
yeah just... I'm curious about that
Lisa: you know it's easier...
what can I say... I'm senior... I work my butt
off... I played by the rules of the game. I
have this fancy position
so like... and actually in the University
of Washington actually for those of you
looking for graduate programs,
University of Washington has a
latina queer president.
so most of them do live in this bubble.
Melissa how do you...
how do you see that?
Melissa: okay so I...
i think this is a really really
important and interesting question
and the what comes to mind for me is
so... I...I pass is white in a lot of spaces
and so with that comes
the white privilege right and
and i think in terms of what i was
talking about before that bridge
that bridge spanner that boundary
spanner
is using that privilege that i have
to step into those spaces and so you
know i'm
i am queer i am indigenous so i i do
benefit from a lot of light privilege
and
which means that i have a voice
that is heard more than
maybe my black and brown um
and black and brown lgbt
you know community members and the way
that i acknowledge and use that is by
you know opening up that space to share
um so that those voices can also be
heard
so you know i feel i feel in my space
and where we are in this kind of bubble
that we're that lisa and i were talking
about a little bit
um that you know i
i take up as much space as i can already
um and i do that for the benefit
hopefully
of others who who have even less of
that space than i typically would um
because if you know if
unfortunately we're in systems now
that that kind of allyship is necessary
in order to
have that kind of equity in terms of
whose voices
are heard in that process so
hopefully that that helps you know to
think of it of that kind of a question
in a little bit of a different way
yeah thank you yes
we have a comment in the chat box if you
can actually
perhaps comment on that
it says as an engineering graduate
student my parents who are both
engineers have actually been the ones
who have encouraged me to hide my
identity
of non-binary in order to be taken more
seriously
professionally i'm still not quite sure
what to say
to them about that
oh you know that's so hard they love you
you know they want to take care of you
they want to protect you i think
um i wanna
i think i wanna say it's gonna be a
journey for you
and the degree to which you can hasten
the ability
to work into your full
beautiful non-binary identity
in the workplace is going to make a
difference in
not just your own mental health but the
quality of the engineering you do
find find your
community of mentors and just
keep taking the baby steps and
take them along with you it's it's gonna
be
it's gonna be hard they're doing it out
of love they're scared
but don't keep going keep going
because you're beautiful you gotta do it
well with that thank you so much
lisa and melissa for this extremely
touching and amazing dialogue i mean
if we had time i could do this until the
morning i'm quite honest with you
but uh thank you so much uh this was so
touching and so inspiring
and um yeah i hope you enjoyed the rest
of the conference and
i look forward to personally get in
touch with you because i was still
touched by your dialogue so
thank you thank you so much for your
time thank you so much for
inviting us and lisa it was really
really great to have this discussion
with you thanks
melissa thank you for this and for all
those conversations we had in the past
in the future
and to the community out there this
international community
take care of yourselves support each
other
you know your science needs
okay thank you hi everybody thank you so
much lisa and melissa hi
thank you thank you all right
with that we are going to move on switch
gears
and our next speaker is serena
lautrec from michigan state university
and i think serena is here
right yes hi awesome hey how are you
all right take it away all right um wow
i
lisa melissa that was incredible i feel
the most
you know whole and grounded that i think
i really have since the beginning of
quarantine so
um thank you again for that uh let me
just
share my screen here
all right can i get a confirmation that
you guys can see both my presentation
and the
closed captioning yes
excellent all right so um my name
is serena lotrick and i she her pronouns
um and i'm a graduate student
at michigan state university i'm in the
plant biology and computational
mathematics science and engineering
departments
um and today i'm going to talk to you
about domain specific
knowledge graphs in plant biology
so uh just a quick overview of my talk
to keep you
grounded in in kind of what's going on
here the first section i'm going to
talk to you about why plants so i plant
biology
in the second section i'm going to talk
to you about a computational technique
called knowledge graphs
and in the third section i'm going to
kind of put it all together and there'll
be little boxes in the
upper right corner of the slides to kind
of keep you on track with this overview
so the first question right why plant
biology
the simple answer is that by training i
am a plant biologist
i think plants are just the most
fascinating um diverse and interesting
biological system that's out there
totally my personal bias but also
right plant biology is the cornerstone
of our modern agricultural
system and and as i'm sure we're all
aware
right climate change uh threatens this
agricultural system of production
through things like drought and elevated
co2 and increased temperatures
but also one of the lesser talked about
ways that climate change will impact our
food is actually through pest management
so in the current day and age we lose
about 40
of our global crop yield to pests every
year um and this is with pest management
techniques such as pesticides and
engineered resistance of plants um
however both of these techniques are
going to be affected by climate change
the toxicity of pesticides is projected
to decrease
while the resistance of pests to these
pesticides and also engineered
resistance mechanisms
will increase and so for this project
i've chosen kind of a small
sub-discipline of plant biology to focus
my first efforts on
and i've chosen the growth defense
trade-off of plants
and so this is the idea that defending
oneself
from insect herbivores is an
energy-intensive process and it directs
energy away from other
important functions such as growth but
in order to have high fitness you need
to both grow
and defend in order to have enough
biomass to produce seeds
to make your next generation and just to
clarify in this diagram
the acronyms that you see inside the
arrows those are actually plant hormones
and systems that regulate this trade-off
through crosstalk so
these hormones are involved in pathways
that control one another
in order to balance this trade-off all
right so switching topics a little bit
i'm going to tell you about knowledge
graphs now and to motivate
this technique i'm going to first tell
you that there are 50 million
scientific articles and counting in
publication in the world today
and that is way too many for any human
being to read in their lifetime and i
know you're looking at me and you're
saying serena
those don't all have to do with you
right some of those are about
engineering
or about human biology or what have you
however it doesn't really get much
better um if we look at specific
disciplines so
pubmed is a search engine for uh
biological literature
um and if i put in the search term plant
biology i get 150 000 results again
too many for me to read in one lifetime
narrowing down even farther
flowering time is a well studied
subdiscipline of plant biology
looking at when and why plants flower
during the growing season
and if we search flowering time we get
16 000 results
and if i look at plant defense and
growth which is a little bit of a
younger field than flowering time
i still get 10 000 results and now
there's so much information that is
buried in this
ginormous pile of literature
and the only way we have right now to
get at that information
is to read individual papers and it's
very difficult for us to read large
numbers of papers
to retain the information that we've
read and make connections between papers
so we might ask right can computers help
us read the literature right computers
tend to be faster
at everything than we are so first i'm
going to give you a few definitions
uh the first is machine learning so
algorithms that learn from the data and
when you present
a machine learning algorithm with a set
of data it looks at the patterns in the
data and learns to make predictions
based on those patterns
and then natural language processing or
nlp is the field of computer science
that deals with extracting meaning from
human language texts
and this field relies heavily on machine
learning
so with both of these definitions under
our belts now can computers help us read
the literature and the answer is both
yes
and no so imagine that we have our
little happy-go-lucky
machine learning algorithm here right we
present the algorithm with a text
and in that text is a sentence like when
the hammer fell on the glass table
the table shattered great good hammer
breaks the table right we understand
exactly what's happening however
if we change the sentence to when the
hammer fell on the glass table
it shattered what is it and to you and i
right it's extremely obvious that well
of course it was the glass table
right because if your hammer breaks upon
contact with a glass table i think you
have some other
you know parallel universe kind of
problems
but our algorithm is kind of confused it
doesn't know how to contextualize
the information encoded in it in this
sentence
um and so it has a hard time parsing the
meaning of this sentence
so the conclusion here is that while it
is difficult for algorithms to
understand the nuances of human language
there has actually been a lot of
progress in the field of nlp
and algorithms can most certainly help
us out
and so one of the ways in which
algorithms can help us out
are knowledge graphs and so a knowledge
graph is simply
an information representation of facts
um
and it's just a set of uh entities which
are represented in this image by ovals
and relationships which are presented by
represented by arrows right so you can
see that this is
um previous united states presidential
administrations
right and for example we can see the
relation first lady
connects the clinton administration with
hillary clinton
but if we look at the obama
administration and michelle obama there
is
no relation in the graph for first lady
and this
is most likely because either there's
noise in the data and
that information got lost or it's not
explicitly mentioned in the text that
was used to build this graph
but the beauty of this technique is that
you can actually infer
these relationships and i'll talk about
that in a little bit
so there are two major steps in building
a knowledge graph
and the first is information extraction
which is composed of several smaller
steps
so the first one is named entity
recognition this
is where we go in and we look for all
the names that are in those ovals in the
graph
so for example in the sentence hillary
clinton is the first lady
of the clinton administration hillary
clinton
and clinton administration are both
named entities
the next step is entity resolution so we
want to be able to
to determine that hillary clinton
hillary
and ms clinton all refer to the same
underlying
real life object which in this case is
hillary clinton
and finally we have religion extraction
this is where we get the relationships
between the entities so
for example in this sentence first lady
is the relationship between hillary
clinton
and the clinton administration so once
we've done all of that
we get a set of triples which are of the
form head
relation tail and in our example here
the triple is hillary clinton
first lady clinton administration
now while a knowledge graph is
essentially just a collection of these
triples
there's one more step and that is
knowledge graph completion and this is
performed to both
clean up the graph remove any incorrect
information
and also to infer relationships that may
be true
and we do this by a process called
knowledge graph embedding
um so to illustrate this imagine that we
have a set of axes now what we're going
to do
is we're going to represent the head and
the tail as vectors on these axes
so in this case down here i have obama
administration and clinton
administration
and up here i have michelle obama and
hillary clinton now the amazing thing
about this technique
is that words and entities tend to
cluster together by meaning
when you represent them as vectors i
still find this to be extremely magical
um but it's extremely useful so now we
can represent our relation
as a vector translation between the two
sets of entities
and so since we have explicitly present
clinton administration transposed onto
hillary clinton by the relationship
first lady
we can infer even if that link is not
there in the text
that sense the obama administration is
transposed onto michelle obama by the
same relation first lady
we can infer that the relationship first
lady holds between the obama
administration
and michelle obama so once we've
performed this process
we end up with our completed knowledge
graph which has our inferred
relationships
present and today i'm just going to talk
to you about my work
repurposing named entity recognition
tools for plant biology
so named any recognition tools there are
many of them
and that are available the nlp community
is absolutely prolific in creating these
robust
um and very accessible tools um to do
entity recognition so
this is just a snapshot of the beginning
of the wikipedia page for obama
um and each entity is outlined with a
box
and the color of the entity and the bold
text next to the entity
just refer to the type every model
named then it be recognition model has
several types
which it places the entities into
categories and so you can see that
this works exceedingly well on this type
of text right we identify
obama and we identify both spellings of
his name
we identify illinois and the united
states in both
the abbreviated and the full spelling
and we also successfully identify the
democratic party
as an organization however if you're
to apply this to scientific texts
especially plant biology text we start
to run into some problems
um so this is an excerpt from an
abstract of a paper
um and as you can see we've got some
weird stuff going on
right so we've identified gibberellic
acid which is a plant hormone
and brachiopodium de sachin which is a
plant as being people
we've identified these acronyms that
stand for hormone names as being
organizations
this one is my absolute favorite we've
identified
the chemical methyl jasmonic acid as
being a work of art
for those who may not be familiar this
is what methyl jasmonic acid looks like
and we've also failed to find the
entities ethylene and salicylic acid
which are quite important
entities in plant biology now there are
entity recognizers that have been
trained on biomedical text which is
about the closest we can hope to get
with a pre-trained
tool and while these tend to perform
better than the general models
um they still don't quite do what we
want them to do
so as you can see right we've identified
ethylene and salicylic acid but also
some funny stuff is happening right
wheat genome is identified as two
entities when clearly
the wheat genome is one
so uh future directions for this project
in the short term
are to retrain these existing tools not
just for named entity recognition
but also for entity resolution relation
extraction
and knowledge graph embedding in order
to obtain high performance on plant
biology literature
and i'm starting in the molecular
discipline in order to
get a good footing in retraining these
tools repurposing them
so that for my more ambitious long-term
goals
i can create graphs that link biological
information on disparate scales
so what does that mean right um if you
consider kind of the different
fields that we have in plant biology or
in any biological discipline right they
include things like ecology population
genetics
molecular genetics and biochemistry
right now these
fields look at different aspects of
systems
right they're oftentimes studying the
same thing for example the growth
defense trade-off
actually was an ecological topic before
it was taken up by molecular geneticists
and biochemists
however if we could create graphs that
link information across these scales
we can synthesize understandings of
systems as systems
rather than as individual aspects of
these systems and this is what i'm the
most excited about
um with this project and then another
long-term goal
that i'm also so super stoked about is
um
evaluating misinformation president
present in published literature
now we treat published literature as
fact um
however there is a lot of conflicting
information in the literature and that
doesn't necessarily mean that there's
misinformation present in certain cases
it could be the way that something is
phrased or the way that a study was done
um but knowledge graph embedding and
knowledge graph construction can be used
to kind of evaluate
what information may be true what
information is conflicting
um and hopefully we can kind of delve
into what's happening there in order to
to create a body of literature that is
more robust um and
hopefully in the end more true
so with that i would like to give a huge
shout out to my lab for being super
supportive especially
my advisor who with whom i've been
working very closely on this project
and also to my funding source for this
year which is an nsf training grant for
plant and computational sciences
and with that i will take any questions
awesome thank you so much serena for
that wonderful talk
um do we have any questions from the
audience or
the panelists
i think uh vinod has a question but i
have to take away his
um oh okay perhaps we know
we can just we can unmute
them and
okay vinod i've taken away your
co-host privilege if you do want to
unless i misunderstood i might have
misunderstood
let's see i i don't see a question there
yet but
oh here we go okay
um have you used the global agricultural
concept schema in any of your work
no i have not and i'm definitely gonna
have to look into that because we do
we are looking for um kind of frameworks
to
to decide right like what things are
entities what things are relations and i
think that this sounds like
uh from what i understand as a concept
schema
that it will be very useful so thank you
for that
awesome um let's see if we have
any more questions and what is the
immediate short
term kind of step for your project right
now
yeah so right now what we're trying to
do is to build
kind of a little prototype graph um and
even
on a smaller scale than just the growth
defense trade-off so
um if i actually go back uh
it will take me a very long time to go
back to the beginning of my slides but
if you remember
the figure about the growth defense
trade-off in those hormones there are
actually two hormones jasmonic acid and
gibberellic acid which regulate one
regulates defense
and one regulates growth um and they
have kind of documented crosstalk
between them and so we're hoping to make
a graph that centers on those two
entities and the kind of immediate
connections between them
um just to get a sense of right how well
does this technique work
you know where are the holes in our
pipeline how do we retrain all of these
tools and we actually have
some collaborators that work in this
discipline and so we're going to
kind of work with them to evaluate the
graph when it comes out
you know is there information present in
the small graph that they
you know off the top of their head
haven't seen before um
or you know stuff like that so
that's kind of what we're excited about
we're hoping to to publish on that soon
awesome all right so thank you so much
serena for this wonderful talk
and uh if there are any more questions
actually i see one more question but
we will send it to you uh after the
symposium uh
all the unanswered questions thank you
so much all right thank you
moving on our next speaker is david
lydon
from university of pennsylvania um is
david
here uh sure am can you hear me okay
yeah we can hear it all right take it
away perfect um so let me share a stream
and um i'll also be talking about
networks so serena thanks for your talk
for um teaming me up um so
i'm gonna be talking about knowledge
network building and its association
with deprivation curiosity
um so just to give you a bit of
background um
first i just want to acknowledge my
co-authors and the funding associated
with the project
um and also um the stem village for
putting on such an amazing
event today um and so i'm interested in
curiosity which we're going to define
here
as a propensity to seek out novel
complex and challenging
interactions with the world people who
are high in curiosity
tend to also be high on life
satisfaction and well-being
and this association between curiosity
and well-being is often
often interpreted by um findings that
states of curiosity
produce novel and broad-ranging thoughts
and actions that build into resources
that
um uh lead into our well-being so if
you're someone who tends to be curious
you're doing novel and challenging
things learning new skills
that help you when you encounter
challenges in the future
but we have we know very little about
what curious practice
actually looks like so what does it look
like when you're being curious and
practicing curiosity
and what exactly are the types of
resources that are collected
when you're practicing um curiosity so
trying to
open the the black box of this idea of
resources that are
being collected and the reason that we
don't know that much about this
is because the information seeking that
we do when we're curious is very
open-ended and it's very idiosyncratic
um so the goal here is to create a
method to open the black box
of curiosity um so to do this we take a
curiosity as knowledge network building
approach in this
perspective we think of knowledge as a
network
where the nodes or the individual units
of a network
are discrete concepts and then edges or
lines are shown between nodes if they
are similar
if they're concepts that have similarity
between them
and so i want you to focus on the two
different networks that you see here
um and i want you to imagine that a
person is acting on their curiosity
they've gone out
and they've gone on an information
seeking expedition
and both these people have created
knowledge networks
they both have the same number of nodes
in their networks so they both
encountered the same amount of novel uh
concepts
but they look very different in terms of
the amount of connections that are
between the concepts
so for the person on the left their
network is um
has sampled very diverse concepts so it
has a loose
kind of organization with very few edges
between the
concepts whereas a person on the right
has sampled closely connected concepts
so they've created a very tight network
and we call these busybodies and hunters
that's because of work by dr perry zern
he's an assistant professor
of philosophy at american university um
and he's identified these um two
different styles that link onto this
idea of tightness and looseness
by looking at how curiosity was used
throughout you know
a ton of literature um but for now these
are just useful labels
um you can think of them as ranging from
a dimension of tight to loose knowledge
networks
so this is all very abstract so we want
to see if we can operationalize
this idea in a specific instance of
knowledge network building
to do that we recruited 167 participants
um here are the age gender and race
ethnicity breakdowns
they came into the laboratory and they
completed a baseline survey
where we got demographic information but
also information about curiosity using
standard personality surveys
and then for every day for 21 days they
completed 15 minutes of a knowledge
network building task
and the reason we did this for 15
minutes every day for 21 days
is that we could get lots of data on
each person so we have over five hours
of
knowledge network building for each
individual
um to give you some more information
about what that task was
we essentially asked people to go onto
wikipedia every day
for 21 days for 15 minutes each time
the task was open-ended they were simply
asked to read about whatever they felt
like reading
so we were trying to get at this
intrinsically motivated information
seeking
that often is embodies curiosity
so they could read through pages they
could use a search bar to get new
concepts they could open up new tabs
they could click on links
as long as they stayed on wikipedia for
the 15 minutes that's all that we asked
them to do so uh we also recorded
um the pages they visited and the order
in which they visited them
so that's the data we're working with
what is the page you visited and what
order did you did you visit it
in and so we have
these the sample visited over 18 000
unique wikipedia pages so it's
a lot a vast amount of data and so now
we need to find a way to take um
to take this from uh just wikipedia
pages um to a knowledge network that's
going to give us insight
into um the type of curious practice
that people are doing
so to take wikipedia and make it into a
network the nodes
of the network can uh are represented as
the individual pages so each page is its
own
uh standalone concept so here you're
just looking at the wikipedia page for
dog
and the wikipedia page for philadelphia
so those are two units
that will make up a network but now we
have to quantify
the edges or the similarity between
these two pages
and the way that we did it was by
quantifying the similarity between the
text across
all of the 18 000 plus pages
more similar the text that was within
each node
the stronger the link between the two
pages
was but the idea being that if the text
is similar then they're probably
exploring similar concepts
and so now for each person if you just
look on the right this is just an
example of what
an order someone might have gone through
wikipedia and they would have started
with mary marikiri pierre kiri china and
then beijing
so we have the pages and the order in
which they were visited but now we also
have um the strength of this
association between these um different
um concepts
so the link between mario kiri and
pierre curie is strong it's very similar
but it's not that strong between pierre
curie and china
so one thing we can do is we can simply
take the average of these
jumps so how big or small the jumpsuit
they're taking
to get an average edge weight for each
person in our sample
we can then represent that as an average
edge weight distribution
and so people on the lower end of this
average edge weight
they are practicing curiosity in the
style of the busy body they're making
big conceptual leaps as they move from
page to page
whereas people on the right tend to look
more like the hunter they're making
small
conceptual leaps as they move from page
to page
but is this actually working as we think
it is
so one way we can do that is just look
at examples from the left hand side so
an individual who should
be making big conceptual leaps as they
move from page to page so here's just a
couple of pages from one individual
who would be classed as a busybody they
started out physical chemistry they then
went to the v2 movement they then went
to the partridge family
then uh to a page about a primary school
in england for some reason uh and then
to hip 79431 which it turns out is the
star
um and then to a page about a race car
driver so you have this kind of diverse
seemingly random list of concepts which
tracks with what we were expecting to
find at that lower end
of the distribution in contrast we can
look at someone who should be making
smaller conceptual leaps as they move
from page to page and look at someone
with a relatively higher
average edge weight and this is just one
example of a
couple of pages um from an individual at
that end of the
distribution and this person looked at
the history of jews in germany
and they then went and read about the
hip-hop riots so
um an event in jewish history um they
read about zionism and then some other
jewish thinkers and so you can see that
it has much much more closely connected
concepts on this side of the average
edgeway and then
you might be wondering about this person
all the way over here um so they're a
clear outlier with
the highest edge weight of all the
networks that were created
out of our 160 people
and this was like a beautiful proof of
concept because this person should be
visiting very similar pages as they move
through wikipedia
and that's what we find so this person
we're calling a super hunter because why
not
um and every page they visited had
something to do with the british royal
family
so they read about elizabeth second
george sixth
uh edward eighth george fifth and the
only page they visited
um that wasn't about a member of the
royal family was about a ship
that was named queen elizabeth ii so
this was a really nice
proof of concept that we were able to
take this kind of vast amount of
information about really open-ended and
complex
idiosyncratic information-seeking
behavior and
quantified in a meaningful way
another way we can see if this is
working is we can ask um
does average edge weight show
associations with existing measures of
curiosity so how we typically measure
curiosity
and so here we're using um a curiosity
scale
that captured between person differences
in curious curiosity at the baseline
survey
um in particular we looked at how peop
how much people
endorsed whether they were high or low
in deprivation sensitivity
so people who are high in deprivation
sensitivity they seek information to
escape the tension of not knowing
something so they hate not having the
whole picture
and so um when people are have this
experience this deprivation sensitivity
they have this determination to continue
information seeking until a knowledge
gap is filled so this results in a
persistent and effortful form
of exploration about a specific topic um
and so as you would expect people who
are higher in deprivation curiosity
are higher in the average edge weight so
they look more like the hunters that was
a really nice
um validity check that we are capturing
something about curiosity as we
think about it um so we can operation
wise curious practice
as a knowledge uh now as a knowledge
network network building practice
um and doing this we can characterize
different types of network structure
um using graph theory to get individual
differences in curious practice
here i just talked about average edge
weight um but we can also use things
like clustering and path length
and these all show meaningful
associations with deprivation
sensitivity
and so by doing this we're opening the
black box of what the resources that are
being collected
during uh curious practice are which is
going to help us detail the link between
curious practice and well-being
in future work so that was just a taste
of the project
um you can find more information
with our preprint on sciarchive which
actually just got accepted yesterday
which i'm really excited about
and you can also check out my new lab
that i just set up in the annenberg
school for communication at
the university of pennsylvania and
thanks
thank you so much david for this amazing
talk
um do we have any questions from the
audience
or the panelists i have a question but
maybe i can just go first while the
audience is thinking about that
so this might be irrelevant so if it is
please feel free to call me out but
um is there something about what you're
working on in terms of like the
depreciation curiosity and the
like being a hunter and so on and so
forth and the online radicalization that
we see now right on youtube for instance
right
if you follow like right-wing videos or
alt-right videos you
kind of enter a path of like just
self-radicalization right
have you looked into that or do you have
plans to look into that and how that's
associated with the type of behavior
that you're studying
yeah that's a really interesting
question and it's something we're hoping
to look at next so
we use wikipedia which is actually very
different to anything else on the
internet right now it's not it's an open
encyclopedia
it's not for profit it doesn't
necessarily lead you down certain
avenues of exploration but there are
other websites out there
that kind of put you on this pathway um
and encourage you to kind of keep
delving down into a topic until you end
up in an information silo like the type
you're you're suggesting
and so um the next step is to look at
how different platforms so not just
looking at people on wikipedia
but looking at people across different
platforms to see if different
platforms would encourage more or less
hunter busy body like behavior
yeah great question yeah absolutely i
think that would be really interesting
actually i realized that just
with my own habits right like on youtube
like it just keeps me kind of like
within the same kind of i guess like
equi-chamber a little bit
like i mean i i find comfort in it but
i'm just curious to see how you can
study that and i would be super
interested in
seeing the results for that yeah he does
but just before that
would be that sort of that typical white
man with i've got a comment not a
question
but it's literally just to say i think
it's so
amazing that you can that you can study
curiosity
in a quantitative way my mind is just
blown by that i think it's
so cool but anyway fine with that
question
i was just wondering if well two
questions actually um the first one was
to see
if if it's possible for someone who has
more of a
busy body behavior to them become a
hunter and vice versa
and the second question is um is it
possible to identify potential patterns
within the busy body behavior that we
are not
at first looking at and then may explain
that sort of
seemingly random um you know kind of
curiosity pattern yeah great questions
so
um here we're kind of thinking about
we're i'm talking about them as if
they're two
binary things that's of course not the
case some people
who um it's kind of a long continuum of
creating
uh type versus loose networks right um
and
what we found which i didn't present
today is if you just break down the
21 days into uh three week periods and
you create a network for each person for
each week
there is fluctuation in the extent which
a person is
would be considered like a hunter or a
busy body so there is fluctuations in
the extent to which a person is going to
express um going after like
tightly related concepts versus loosely
related concepts
and um we also collected daily diary
data alongside this
task so one of the questions was asking
about people's sensation seeking so the
amount
uh the extent which during the day
they're going after
new and exciting and novel experiences
and so on on
during weeks where they were going out
into the world and experiencing
new things on those weeks they tended to
have more of the busybody
uh like um structures which suggest that
um kind of in line with your second
question it's like maybe these are just
really
different thing that things that they've
experienced during the day that week for
example
that would explain how they're making
links between these concepts
that aren't in the investigator's mind
or in the mind of the algorithm that's
saying this page is similar
this one is not
um yeah and i guess also asking we
didn't ask the participants here so
with reference to your second question
they may see a train of thought driving
this disparate search um that we're not
getting at by relying on a computer to
tell us what's
similar or not so that that's a really
interesting um way to think about it one
way we're exploring that
is um we're interviewing an artist who
tends to integrate um
uh very different ideas at least on face
value
but in talking with her about her
process she tends to um jump back and
forth
um uh jump back and forth but there's
meaning behind why she's making those
jumps
and so that's rebecca came in just for
anyone who's interested in the art side
of things
cool thank you
awesome all right if there are no more
questions
let's thank david once more thank you so
much for the amazing talk and
if there are any more questions we will
make sure to follow up with you
all right awesome there thank you our
next speaker is javier garcia from
university of california davis
uh is javier here all right yes here we
go here
all right take it away search
all right can everybody hear me
yep okay perfect uh hi everyone so my
name is javier garcia
and i'm going to be talking to you about
the work that i've been doing as a
graduate student
at university of california davis i'm
a entering my fifth year in the phd
program
where we study fungal pathogenesis
particularly fungal pathogenesis of the
central nervous system so
um which i'll get into in a little bit
so fungi are the
major we study the major
pathogens that cause fungal meningitis
and so fungi are often
underappreciated for what they do um
especially in mycosis
and so it's more than just a foot fungus
so the disease pathologies range from
mild skin irritation to
disseminated disease which i'll talk to
you about in a little bit
um there's about 1.5 million deaths
resulting from fungal infections but
only 300 out of the 1.3 million species
of fungi are pathogens um
and there's limited treatments to these
fungi or i'm sorry there's limited
treatments
to these diseases these fungal diseases
um limited diagnostics
as well as the basic mechanisms of
disease
and only until recently the fungal field
is getting a little bit more traction
but the molecular mechanisms of how it
causes disease
are still very lacking and so one of the
pathogens that i study
is called the disease is called valley
fever
and so what valley fever is it's a fatal
potentially fatal fungal infection
caused by the coccidioides spore
and it's really important because it's
actually found
essentially in my backyard and so um
it's caused by the inhalation of the
spores that i mentioned um
it's predominantly found in the
southwestern part of the u.s and in
california's central valley which is a
major agricultural hub
so people who work in agriculture
construction are extremely susceptible
to
acquiring this disease and so when
the soil is excavated and the uh the
spores are exposed
people breathing these spores um
and primarily it establishes that as a
lung infection so people
breathe in these spores and the fungi
goes through a morphological change
and so um the chain the
spores change into what's called an
endospore these endospores grow into
essentially a sack of
more endospores called spherules those
spherules break open
and the cycle continues and
it disseminates uh into the other parts
of the body
and so some of those parts oops
some of those parts that um
are affected are so it's a primarily
it's a primarily it's a lung infection
um
and so once it establishes infection in
the lung it can spread to other parts
of the body such as the skin and muscles
the bone and joints
um the lungs like i mentioned and one of
the most devastating parts of the
disease is
infection of the central nervous system
and so
it's classified into three the
manifestation is classified into three
major parts
the first part is asymptomatic where
people have a positive serology meaning
that they
have antigen in their body but they have
no
symptoms of having cocci or i'm sorry
valley fever
and so 60 of the population that
acquires this disease
have no symptoms and so we've we've seen
asymptomatic a lot in the news regarding
covet and so this is a similar
manifestation and so uh people who do
get pulmonary toxicity mycosis
um you'll find in x-ray findings these
calcif these
uh tumor-like uh projections in ct scans
with a positive serology and about 50 to
75 percent of people
have this manifestation and like i
mentioned the disseminate disease is
when
it spreads to other parts of the body um
what about one to five percent of people
acquire disseminated disease and once it
is uh disseminated it's very hard to
treat and if it's not treated it's
100 fatal and so
one of the approaches we want to study
uh
that we're using to study uh the
coccidioides
is to study the proteins that mediate
host
invasion migration migration
adhesion and so on and so today
not much is known about the various
virulence factors that
excuse me that comprise
this organism and like i mentioned
before there's no
there's actually no pathways involved
or there's no pathways identified
involved
in disease and so one of the approaches
like i mentioned
is we want to study the proteins
associated
with disease and the proteins that are
associated
with disease are usually found on the
outside of the cell and so these are
extremely important because they can be
used as biomarkers
vaccine targets more recently
anti-virulence therapeutics where we can
target
just the disease-causing aspect of the
of the organism without causing
evolution or
drug resistance and so um
we want to uh characterize the surface
topology
of coccyx uads and one of the major
focuses that we
want to focus in on when we're looking
at these
large proteomic sets is looking
primarily at
host invasion and cell damage um and
dissemination
because like i mentioned these are the
first
proteins that are going to be mediating
the
interface between the host and the fungi
and so to start what we are using is
we're using a
a particular strain of cocciduity's that
has been
maintained in the parasitic life cycle
so like i mentioned before it's usually
found as a mold in the soil
and when the mold breaks free and the
arthritis or spores are breathed in they
undergo this morphological change
in the lungs and so we have a strain
that remains in this morphological state
this sphero endospore phase which i'll
call the se phase
um and it's been maintained since the
60s and so it's
really important because we've
demonstrated that
it's still virulent despite being
cultured for
over 50 years um it's we're able to
compare the proteome of this
laboratory strain with the parent strain
that it came from
and it facilitates our studies because
it's also a bio safety
level 2 pathogen so there's no
arthrocanadia stage where
a person could breathe it and so it's
easy to grow there's no need for
bsl3 equipment
and finally it's this sc stage is the
disease state that's found in the host
and so it's really important that we
have this strain to study and
begin our surface proteome studies
so essentially one of the techniques
that we're employing
is a them a method called trypsin
shaving
and so trips and shaving um essentially
you treat your cells with trypsin and
the trips and cleaves at
specific residues on proteins and so
we're able to
collect the cleaved proteins concentrate
them and we can run them on a gel
and so what why we want to run it on a
gel is because we want to see different
differential banding patterns with two
different treatments
so pbs is just a normal buffer we don't
expect to see any cleavage or proteins
and with trypsin we're expecting to see
proteins that are are cleaved off the
surface
we can then take those proteins and
sequence them
using mass spectrometry and we can
analyze what those proteins are
and so when i did that we were testing
different conditions
and we were able to see that in the
trypsin treatment we saw
a differential band that's about
40 kilodaltons in size and so
um this band represents something that
is being cleaved off of the treatment
and so we cut that band out and we send
it off for mass effect sequencing
but um you may if if you're familiar
with
cell culture techniques um trypsin is
used to
uh cleave or
separate cells from the surface so it's
a very harsh treatment
and so um we want to make sure that the
trypsin treatment isn't
breaking open the cells and releasing
proteins from the inside because we're
only interested on the proteins on the
outside
and so um this just shows that after
before treatment and after treatment
these cells
um remain mostly they remain intact they
remain the spherical shape
and so um
so that confirms that we don't have any
mass cleavage of cells
with resulting in mass
leakage of those intracellular
and so when we did that we found in that
banding pattern in that band we found
12 proteins of interest and so
these four that are highlighted in
yellow are
have been previously identified in the
literature as immunoreactive and so that
means
the proteins are likely located on the
surface on the outside they're being
secreted
and they have an immune effect on the
host
and so um going back to my hypothesis
which is these surface exposed proteins
um are virulence factors um
that mediate cell damage so they're an
aspartal protease has been known to
cause cell damage
and other fungi um adhesion
um this carbohydrate binding domain
could be potentially involved in
carb adhesion or immune evasion so there
was this superoxide dismutase which is a
protein that's also a virulence factor
in other fungi
and then interestingly these other
proteins that i didn't hide and
highlight in yellow
have cytosolic functions and so in the
literature it's been
noted that there are some proteins
that have dual roles and they're called
moonlighting proteins and they can
perform
functions at the surface that are not i
guess what they're intended to do
and so they can have roles in virulence
and drug resistance and so on but we're
primarily interested in the
immune reactive proteins that have been
previously
been identified but this is only
a really small subset of proteins it's
not representative of
the whole proteome of proteins that are
found on the cell
so to do that we i've essentially used a
more
shotgun approach where instead of
running it on the gel
looking for a differential banding
pattern um
i had i submitted my entire contents
of cleaved protein to the
mass the the proteomic cord to analyze
and so we we can essentially uh compare
that with
our control which is the pbs control and
sort of subtract the proteins that we
see in both
and analyze the specific proteins found
in one
sample over the other and so when we did
that
um we used a
uh a program to
analyze the proteins to find a signal
sequence so
a lot of proteins have a signal sequence
which is destined
a secretion signal to be excreted
outside the cell
and so um in our pbs control there was
about three proteins that did have a
extracellular signal
which comprise about not about 1.1
percent or i'm sorry
about one percent of actual cellular
predictions
but in the trips and treatment um it had
the highest
percentage of extracellular prediction
and so
that further validated that approach uh
with analyzing these proteins
it's a it's a valid approach to study
these
the surface topology
and so using these proteome mixed sets
so you get these long protein listen so
what do you do and so
one of the ways to kind of almost
going back to the network talks we can
put these into a program and analyze
what proteins are interacting with each
other and
we can get a general idea of what
pathways what
general functions these gene sets are
doing and so
with this genotology analysis we found
that
the in the trypsin treatment most of the
proteins
that we found had uh catalytic activity
peptidase activity hydrolase activity
meaning that these proteins are you know
chewing up something and that's very
characteristic of fungi they
secrete proteins outside their um
outside their cell to cause damage to
to survive and digest on the outside and
absorb
the nutrients and so this again further
validated that
the proteins that we're analyzing are
have some sort of
catalytic activity and so
um
and so in studying the virulence factors
we decided to look at one particular
virulence factor or
predicted virulence factor in this case
um
that's also secreted and so we're taking
lessons from another
fungal pathogen which is called uh
cryptococcus neoformans and so that's
the leading
uh organism that causes fungal
meningitis
and so it has the ability to cross the
blood barrier and infect the central
nervous system
and so and there's a lot of research
regarding cryptococcus
and its ability to cross the central
nervous system
but again there's zero studies on
um on constituents and how it can cross
the central nervous system
and so one of the previous papers from
my our lab
they've identified a protein that's able
to cross the learning barrier
and so one of the experiments that they
did before i joined the lab
was they actually cloned in or they put
in this
gene this protein i'm sorry this
yeah they said they put this gene in uh
saccharomyces
cerevisiae so yeast and so
yeast doesn't have the capability of
crossing the blood-brain barrier
but in this graph when saccharomyces
is expressing this protein it gains the
ability to cross the blood-brain barrier
and so we're using this in static model
of the human blood-brain barrier where
we
have our fungi of interest
we co-culture it with a cell line that
represents the blood-brain barrier
and then we can monitor crossing based
on how many
cells grow and cross um
and so with cryptococcus this protein
was
clearly involved in uh crossing the
blurb barrier
and so we were able to do that with a
similar protein
in coxy duties and so we have the
hypothesis that the similar proteins
homologue is going to be able to cross
the blood of impair
however when we expressed this
protein in saccharomyces we found that
there was no significant difference
in crossing compared to cryptococcus
saccharomyces without any
sacrifices with that's not expressing
the protein
compared to saccharomyces expressing the
protein and this is a
cryptococcus that has the ability to
cross
um and so what we conclude is that
and this is a similar graph to this one
where
i extended the the time
the incubation time to see if we could
see a larger effect
however every time we did these
experiments
we had a non-significant result
suggesting that this metalloprotease
this
protein does not gain the ability to
cross the vibrant barrier
so but that's just one protein
so um to conclude we established that
trypsin shaving is a suitable method to
study the surface proteome
and that gene ontology can reveal the
major pathways associated with
the catalytic proteins and so for future
work we
want to assess the virulence of other
potential hits
especially hits that we keep seeing time
open time and time again
with these gain of function assays and
it's particularly important to use these
gain of function assays
because it's a pretty dangerous pathogen
to work with so
we can essentially just take interrogate
one part of the
organism and see assess its
function um and with that
um i'd like to thank the funding for
this
uh for this work all the people who uh
have helped me throughout this process
and
especially for the stem village this has
been a great opportunity
to talk to other lgbtq
plus scientists and i'm very excited to
to know a lot of what you are doing
around the world
and so with that i'll take any questions
that you may have
thank you so much javier for this
amazing talk uh
we have questions so i'll just start
highlighting those
all right so interesting that most ms
identified
peptides are enzymes is there a chance
that
post translationally extracellular
proteins
could not be identified by trypsin
treatment since
acetylation could often acts act as
a signal to interact with host proteins
so that's a great question and so um
there's not much known about the
post-translational modifications
in coccydoids and so one of the
but one of the things that we do see at
least in these protein sets is we do see
a lot of glycosylation
enzymes and so we know that
the surface of the cell has a lot of
like oscillated proteins but what their
function is we
really don't don't know and so that's
this at least opens up some of the
research or opens up some of the more
work for us to understand what is what
is going on at the surface
does that answer the question awesome
uh i think uh cameron has a question
cameron go ahead hi um yeah that was
really interesting um
i never mastered on parasites and the
fact that it was a moonlight and so i
thought were really cool
my question is however you showed a map
of the distribution
um it's really similar to west nile
virus i'm just wondering
is the effects of climate change causing
a greater spread
of um cochlears and therefore an
increased incidence of
infection yes so that's a
great point um so in california
we have been experiencing a lot of
drought and
the cases have actually been
increasing over the years which is
something that we
don't want to see and so we there's a
lot of
um there's a lot of i guess looking
a lot of people have looked into how
climate change has affected
um the rates of infection and so
i would say that climate change does
play a big role in the number of
infections especially when it's found in
an arid climate
the more arid it is the more
um the more uh
fungi are able to grow in the soil i
guess does that answer the
your question uh yeah thank you
yes yeah okay all right last question
uh i'll be interested to hear if you
think unknown violence
mechanisms similar to these might also
be found in spore forming bacteria
so the mechanisms of actually
i don't know much about the other
virulence factors in
sport forming bacteria especially when
it relates to dissemination but
um in our lab we also studied receptors
on the host side and so these receptors
are actually
found are used by a variety of different
pathogens
and this is in regards to crossing the
blood-brain barrier
and so a lot of so the fungi
um parasites like um malaria
i can't think plasmodium falciparum um
several
other
bacteria are able to use the same
receptor and so that kind of suggests
that there's a similar mechanism being
used by
bacteria as well awesome thank you so
much javier for this amazing talk
so yeah i think yeah we just
let's move on to the next talk thing so
our next speaker
maybe the final speaker uh is arthur
sinoko from university of puerto rico um
is arthur here oh awesome all right
arthur take it away
hey thank you you hear me yes we can
hear it all right
thank you well thank you for this
tremendous opportunity to um
to present here for the same village
symposium
so i'm going to share my screen
can you see my presentation yep all
right
okay so today i'm going to talk about
work that i've been doing in my
laboratory
over the last few years funded by an nih
sc1 grant
the title of my talk is synergizing
titanium and iron chelators to decrease
the bioavailability of iron and cancer
cells
so in my laboratory we focus on iron
because we are interested in looking at
a method to
a broad drug design where we can target
an agent that is responsible for the
proliferation and potential angiogenesis
of
cancer cells and so one of the things
that we have really been
keen on is trying to explore ways in
which we can attenuate the
bioavailability of iron within cancer
cells
and that is because cancer cells have a
greater demand for iron than normal
cells
so we just want to give you an overview
of
how iron enters into the cells and this
idea of a homeostatic balance of the
iron that goes within the cell and
is exported so there's an important
protein called transferrin that exists
in our blood it's present
at about 30 micromolar it binds two
ions of iron iii and then
it gets recognized by the transfer
receptor and that
triggers a process known as endocytosis
um
a combination of acidification and also
a reduction event
results in the iron being released as
iron two plus
being shuttled out of the endosome via
the divalent metal transporter
and so then that forms into a sort of a
uh
this uh dynamic equilibrium of a labile
iron pool
part of that pool gets distributed to
the protein ferritin
which will store the iron a significant
amount of that iron gets
utilized um for instance a protein
called ribonucleotide reductase
is responsible for the building blocks
that leads to dna synthesis
but they're also a certain amount of
that iron that gets exported out of
the fair important protein and so what
we have is this balance between the
amount of iron that's going in the cell
that's iron three and the amount of iron
that gets
released what we see in cancer cells is
there's a loss of this balance
and so we have a number of cancer
hallmarks
that are due to this dependency on iron
this higher requirement for iron
we have an overexpression of the
transfer receptor because there is a
need for more iron to be brought in
there's less export of the iron there's
less storage far more utility so we also
see an over expression of iron dependent
proteins like ribonucleotide reductase
so there has been great interest in the
use of iron key layers for anti-cancer
therapy
a number of iron 2 and iron iii killers
that have been designed for other
applications for instance
iron overload diseases are being
repurposed as potential anti-cancer
drug agents so they operate via a number
of proposed mechanisms
some can prevent iron uptake in cancer
cells so this is an activity that is
extracellular
some can deplete iron from cancer cells
others remove iron from sites that
regulate
cell function and there are those that
inhibit iron dependent pathways without
necessarily removing iron
from the cells collectively these
mechanisms contribute to
decreasing the bioavailability of
functional iron
so um in our talk we're going to look at
to an extent at
an effort that has been done to deplete
an iron dependent pathway
so i mentioned ribonucleotide reductase
this is an enzyme that is iron dependent
and it catalyzes the conversion of
dioxide diphosphates to deoxynucleotide
diphosphates
essentially the building blocks for dna
replication
and repair so
the structurally the enzyme is a dimer
of dimer so we have this
alpha 2 dimer constitutes the r1 unit
so it's the bigger component of the um
this enzyme
it contains the catalytic site and you
have this other component the beta2dimer
which is referred to as the r2 unit and
this has a very important
dye iron cofactor site which is
responsible for the generation of an
important
tyrosine radical because the chemistry
that's involved here is a radical
induced process
so the radical is initiated in this um
in this
beta 2 site and it gets shuttled to the
r1 site when a substrate enters into the
into the actual catalytic site all right
so i just want to highlight here
um the dye iron cofactor site
and so when the iron binds into the site
um the iron actually goes in oxidation
events so we transition from iron to
plus
in the reducing environment of the cell
now it gets transformed to iron three
plus
and in that process it actually affects
a nearby tyrosine
and it converts it into a tyrosine
radical
and the very interesting thing is that
we can actually monitor
this particular radical using a
technique called electron paramagnetic
resonance
this particular radical is epr active
and so we can actually
detect this there are a number of
specific
r2 inhibitors and within this family of
inhibitors of this particular enzyme
there are a number of iron chelators
that have been explored for this
potential
capacity so in my work what we tried to
do is fuse iron chelation
using some of these strategies that have
already been explored but coupled that
was titanium
so there's another metal that we're
going to talk about in a moment the idea
is that we want to inhibit the um
the bioavailability of iron for an
anti-cancer application
so why do we incorporate titanium into
our drug design
well interestingly titanium 4 shares
many
similar chemical properties iron iii and
as a result
titanium can bind to many of the same
biological ligands
it has been observed that titanium in
blood when it's actually released in
blood um
it's bound by serum transferrin and this
protein as i mentioned previously is the
protein responsible for the cellular
uptake of iron three plus
and is believed to potentially play a
role in the transport and
biodistribution of titanium in
the human body so via that interaction
titanium
is not believed to be toxic however
depending on the coordination chemistry
now that can then
fine-tune the activity of the titanium
where titanium can then become highly
potent anti-proliferative or cytotoxic
species
and in this vein it's believed to be
able to exhibit these properties by
potentially inhibiting dna synthesis
inhibiting certain
key intracellular proteins and has been
shown to
cause apoptosis at any phase of cell
division so
we seek to exploit this property of
titanium
something that is not necessarily um you
know in our bodies necessarily toxic
but exploiting the coordination
chemistry to take advantage of that
potential
and coupling that with iron chelation
and so what we've been interested in
doing is
looking at how serum transparent
coordinates
iron and titanium to give a structural
insight into potential ligands that can
help us to
design titanium compounds that then
within the cellular environment
can release the titanium and essentially
become weaponized
and so we've actually have solved the
crystal structure
for titanium um being bound by the
transferrin
protein and uh there are similarities
with with with how the iron is bound
but it's also some key differences which
i'm going to highlight here so this is
what was referred to as the canonical
form of how metals are believed to be
bound to this protein
where iron is coordinated to just four
amino acid residues
two tyrosines an aspartate a histidine
and there is a synergistic anion
carbonate which helps to satisfy the
coronation the metal
and helps to stabilize that metal the
binding of the iron actually induces a
a major confirmation change that
stabilizes proteins actually
helps to be recognized by the transfer
receptor
well the titanium there is an important
difference and that is that
it's believed that a small molecule
present in our blood citrate
can help to shuttle the titanium to the
protein but also serve as an additional
synergistic anion that can help to
stabilize the metal balance protein
the presence of this citrate essentially
blocks
binding of the aspartate and the
histidine and it results in some
important differences in terms of the
coordination to this protein and the
changes that are associated with this
protein
nonetheless believe that the protein is
able to to transport this metal into us
into our cells but what we're actually
interested in is
focusing on the key coordination
features and
exploiting this difference in ligand
affinity for a potential therapeutic
effect
and so we've been focusing on small
molecules
that are chemical transferamimetic so
here we're highlighting again
the coordination of iron to this the
metal binding sites of serum transferrin
and we've identified a number of small
molecules
that can mimic the coordination of the
protein to this
metal so for instance uh to the right
here
we have this ligand um abbreviated as
hbed is a hexadentate ligand which that
means it can coordinate
iron at six different sites and it shows
very similar coordination
um modality as transferrin
and then to the left we have uh another
small molecule
the ferrocerus it is a tri-dentate
ligand
this particular molecule is used for
um commercially as a
something that can treat iron excess
and so when it coordinates to iron you
require two of this molecules to satisfy
the coordination
of the metal both of these form
iron complexes that are a very high
binding constants
but what we would like to establish is
we would like to use these ligands to
prepare titanium compounds
these titanium compounds being bound in
a manner that's very similar to the way
the iron is bound
but the idea is that we want that these
compounds be
inert in the outside of the cellular
environment but once entering into the
cellular environment
then a process known as that we refer to
as trans metallation is induced
due to the interaction between the
titanium chemical transferamimetic
compounds
and the label iron pool that's present
within the cellular environment so
here's just a
cartoon representation of this process
so the the label iron pool consists of
dominantly of iron two plus but also
a good amount of iron three
so a number of questions that we've
tried to uh explore
in these recent years is can the trans
chemical transfer of metallic ligands
transmetallate titanium for iron
in the intracellular environment and
if so do these complexes inhibit the
activity
of the iron dependent protein
ribonucleotide reductase
so one of the things that we wanted to
establish in on the bench top was to
just explore this idea of
the feasibility of transmetalation so
here we just have a representation of
the
titanium complex of the ferrous
and what we did was to explore his
interaction with the label source of
iron so we use iron citrate which is a
good representative of
some of a slow molecular weight label
iron iii source and we probe
the potential trans metallation reaction
via a number of spectroscopic techniques
uh one of the really helpful
approaches that we did was use
electrospray ionization qtof mass
spectrometry
to really probe um mechanistically what
is going on and so
what we were able to see so we mounted
to this over the
time frame of hours was that
soon after mixing the titanium complexes
with the label iron3 source we have the
formation of these
ternary intermediates and then those
ternary intermediates dissociate
and they result in the expected um sort
of thermodynamic products where you have
the transmediation event where the
chemical transfer magnetic
ligand releases titanium and it binds
the iron
so what's very interesting to us is that
this is something that
as soon as we mix the titanium complexes
with the iron source
we have immediate reaction but it does
take several hours
until we reach what we would consider
the expected
product but it's very interesting that
we have these intermediates that do form
and so we've explored um this process
for
um for differences but also for the hvac
ligand and other of our chemical
transfer medic
compounds just to get a general sense of
the feasibility of these of the trans
metallation event
so this helped us to to
realize that yes this type of chemistry
is possible but can it actually occur
within cells
so um we had previously characterized
the anti-proliferative properties of our
compounds
and one type of cell lines that these
compounds are quite effective against
are leukemia cells
so we decided to focus on the eurocat
leukemia cells as a case study
to really explore the impact of our
compounds on
the iron within the cells so here i have
uh just a
brief representation of the ic50 values
of these compounds so we see that the
titanium complexes
have a greater potency in terms of
affecting the proliferation
of this particular um cancer cell line
we've also done a cytotoxicity acids to
show that these
compounds are cytotoxic so we do see the
this combination of anti-proliferative
and the cytotoxic effect
a very interesting um observation that
we made was that when we supplement
the uh cell lines so the leukemia cell
lines but also other cells that we have
worked with
with some amount of label iron what we
have seen is that
the cells are now more resistant towards
our complexes
the the pollen see of the complexes
decreases
so what we wanted to explore was if
introducing our compounds to the cells
we have an effect on the iron that is
available to activate the
vibronucleotide reductase enzyme so the
idea is that
here is the the dye iron cofactor site
requires the binding of two iron two
ions and the presence of molecular
oxygen
in order to form the very important
tyrosine radical
the idea is that in the presence of our
titanium complexes
that should in essence make the iron
unavailable or less available and
by making it functionally inert and so
we should
and then be able to observe this by
using electron paramagnetic resonance
what we should observe is a decrease in
the g2 signal that is associated with
the presence of the tyrosine radical
so in order to probe this possibility we
use whole cell
electron paramagnetic resonance study of
probing the your cat cells in the
presence of
absence of our compounds and so here
we're literally
probing the signal the g2 signal that's
associated with the tyrosine radical so
what we observe here is a subset of our
data
this was collected after three hours of
treatment of the cell lines
is the signal that is due to
the untreated cells and then in the
presence of our titanium complexes we
see that the signal
is attenuated it does not go away
completely but we see a significant
increase i believe it's about a 75
decrease for the two titanium compounds
and we see a comparable decrease for
just the uh
metal-free ligands as well so this is
work that was done
in collaboration with professor lisa
thomas at the university of arizona
another interesting thing that we wanted
to explore was the impact of
our compounds on the iron that's present
within cells and so here we were probing
a specific population of the
intracellular iron pool
which is the high spin iron 3 pool and
so
what we observe is a very distinct
behavior between
the h-bed compounds and the difference
versus compounds
so this signal here is due to
the um high spin iron iii in the
untreated cells
in the presence of the titanium
interferoxis or
the metal free differences we actually
see no change in that signal
however for the titanium h-bed or the
metal free
hvac signal we actually see an increase
in this
in this pool so it's clear that these
complexes affect the iron in ways that
are distinct
but nonetheless that impact on the iron
appears to still
be significant in terms of of inhibiting
the activation of the ribonucleotide
reductase enzyme
another experiment that we wanted to
explore
was so we already had previously
established that these compounds are
apoptotic
but we wanted to understand is their
ability to potentially affect the cell
cycle
so we use a flow cytometry as a
as a gauge of understanding the effect
that we can have in the cell cycle and
we did a time dependent study here
so what we have um the top panel
is the effect of the defrosters and the
titanium differences compound over time
and compared to just cells that have not
been treated with anything and
the bottom set of panels we have the
effect of the h-bed and titanium h-bed
complexes
over time and so what we observed was
that
um at 10 hours we start to see that
there is
a cell cycle arrest at the s phase um
and then at 24 hours that becomes
pronounced
for both the metal free diphtheroxis
ligand and also the titanium deforox
compound we observe for
the hvac complexes that at the 10 hour
time point
we also see this arrest of the s phase
but that arrest
seems to decrease by the time we reach
24 hours so there's this time dependent
behavior that we observe but what's very
interesting to us is that this
this data is consistent with what we've
been observing in terms of
the ability to inhibit the
activity of the ribonucleotide reductase
because by arresting at this s
phase we're essentially um is indicative
of an inhibition of dna replication
all right so to conclude we were able to
show that the combination of titanium
cytotoxicity and appropriate iron
chelators in in
this case the chemical transferamimetic
ligands can effectively alter the label
iron pool
and attenuate the ribonucleotide
reductive activity
it appears that the iron chelation by
these chemical transfer
ligands can lead to different changes to
the intracellular iron pool
in our current studies what we're trying
to do is really elucidate the full
details of the
molecular mechanisms involved of um
corresponding to the titanium chemical
transferamimetic
and lithium and cytotoxic behavior what
we're actually trying to look at is
what is that titanium doing and we have
some clues
um but we really wanted to focus here on
on the effect on the iron itself within
the solid environment
so i would like to to thank the many
students that contributed to this
project so a number of
graduate students that were very
influential in terms of the structural
studies and
also the fundamental cellular work
those that have graduated now are
colleagues of the lab former
undergraduate students that have now
moved on to
graduate school the sources of funding
so the one of the major sources was the
nih sc1 grant
now more recently we've been rewarded
with the nhr 21 grant to support this
work
and also very importantly would like to
thank the puerto rico science technology
and research trust grant and then here i
would like to acknowledge the uh the
different members of my laboratory
thank you very much any questions
thank you so much arthur for the amazing
talk so
we do have one question in the chat box
that i can
read does the cell cycle arrest
correspond with epigenetic changes
that may be influenced by iron dependent
enzymes
so we really need to look at this what
impact we have in
the genome also what impact would
potentially having in the program we
have
uh we have not yet explored those on
that particular aspect of the the
medical
mechanism involved, it could be but
we... we
need to do those experiments. We're
actually very interested in looking at
are we actually
in addition to you know potentially
affecting the label or
are we actually directly affecting the
ribonucleotide reductase and that's
something that we're also interested in
exploring.
So we're now expressing this protein to
do direct studies with that enzyme and
see
how is it that we're truly inhibiting
this enzyme so yeah... so
there's work to be done there.
Mehmet: Awesome, let me see if we have more questions.
I think that's it, and I encourage
our audience to reach out to Arthur
if they have any more questions and with
that, we're wrapping up
this session in the symposium, so I think
Matthew
would like to give some closing remarks?
Matthew: Yeah, thanks Mehmet and thank you
Arthur and thank you to
all of the other people speaking in
the session and throughout the entire
day.
I just want to say how
amazing the day has been, how wonderful
it's been to
see not just the Scottish community,
which
was the initial aim of of this event,
but, you know, the global LGBTQ+ STEM
community coming together
and, you know, hearing things that were so
interesting and hearing
things that were heartwarming, things
that were difficult, things that
you know areas where we still need to
work.
It was just it was a really wonderful
event and I just want to thank everybody
so much
for participating so wholeheartedly
and to all of the organizers who
worked to bring this together and to
make it happen.
So thank you very very much and I hope
we can do something again
in the not too distant future, maybe not
quite this long - something a bit shorter -
but I hope we can do future events and
all come together again.
And yet with that, I would just like
to say
stay safe, stay well. I hope you have
a great weekend and thank you very much.
Mehmet: I'd like to... I'd just like to echo
Matthew's remarks and thank you
to Matthew and all the organization
community for leading this effort
and it's been so amazing to connect with
the global LGBTQ+ community
and yeah I hope to see you all soon
in the
very near future again, in another format.
I don't know if anybody else
wants to defend that remark but...
Matthew: Well if nobody else wants to say
anything,
then I guess we can bring this to a
close,
and everybody can can get some rest
we can binge on some Netflix
I'm gonna go eat some ice cream and
watch Canada's Drag Race
Serena: Thanks so much for putting this together it was
absolutely incredible i'm so glad we got
to participate.
Matthew: It's our pleasure and and thank you so
much for participating you know we
couldn't
have done it with... if you know... if people
turned around and said we don't... we're
not interested in talking or
participating then
there wouldn't have been an event so
Thank you.
