>> Most of the people in
this room know someone
with Alzheimer's, autism, or some form
of cognitive impairment.
Sadly, there's no cure or even treatment
for most brain disorders.
A big part of this problem
comes from the fact
that researchers don't fully
understand how brain cells
process the instructions
from their genetic code.
This genetic code is made
of DNA which you can think
of as a cookbook that
contains all the recipes
a cell could possibly make.
From DNA the cell makes RNA
which is a temporary copy
of the genetic material that can
be moved around in the cell.
Imagine RNA as a copy of specific
recipes from the cookbook
that can then be taken into
the kitchen to be made.
Now most people in this
recipe have probably gotten
a recipe from a friend and notice
that there are instructions
scribbled onto the recipe.
Little notes that change
the way the food turns out
without changing the actual ingredients.
For example, when baking
cookies if there's a note
that tells you to melt
the butter your cookies
will be much flatter and harder
than if you had used cold butter.
It turns out brain cells
use a similar note system
to fine tune the instructions
for the recipes they make.
And when these notes are read incorrectly
it can cause serious brain disorders.
My thesis focuses on what these notes
are and how we can decipher them.
Just like writing notes on a recipe cells
can add chemical
modifications to RNA molecules
to change the way those
RNAs are read by the cell.
One such chemical
modification is called m6A
which is depicted by these
blue stars on RNA molecules.
To figure out the function of
this chemical note I deleted
the machinery that cells
use to put m6A on RNA.
Basically I took away the
pencil that the cell uses
to write notes to itself.
When I did this in mice brain function
was severely disrupted
and the mice actually
died shortly after birth.
Now I wanted to know what
these little m6A notes
were actually saying
so I used RNA sequencing
which is a technique
that lets me see all
of the RNA, or recipes,
that the brain cells are currently making
and which ones have notes on them.
I found that RNA with m6A is broken down
a lot faster than RNA without m6A.
It's essentially note to burn
the recipe when you're done
with it so no one can use it after you.
Without this m6A note, RNA just piles up
and the brain cells can't
figure out which recipes
they're actually supposed to make.
Next I wanted to see if
human brain cells also used
this note system.
So I did more RNA sequencing
with human brain tissue.
I found that not only do human
cells use this note system
but RNA specifically related
to Alzheimer's, schizophrenia
and human specific brain
disorders are marked with m6A.
Therefore, I concluded
that this additional layer
of communication at the
RNA level is not only vital
for brain function but could
be the key to understanding
and treating brain disorders, thank you.
(applause)
