UChicagoGRAD Three Minute Thesis Competition: Saurja DasGupta – “In The Beginning Was RNA”

one thing that keeps us alive? My answer would be enzymes. Without enzymes, you would not
be able to eat, drink, see, or even listen to me right now. And the earliest
enzymes most likely coincided with the
appearance of life itself. Those earliest enzymes
were made of a substance called RNA, cousin to
the more popular DNA. In the absence of both DNA or
proteins, in primitive earth, about four billion years
ago, both genes and enzymes were made of RNA. Now, enzyme function is
determined by its structure in three-dimensional space. Just like when I
fold my five fingers, I can do different things. I can signal peace,
rock and roll. I can punch your nose
or shake your hand. So I study structures of
these ancient RNA enzymes to figure out their
biological functions. Instead of shining
light, I shine X-ray beams on tiny
crystals of these enzymes to look at them
in minute detail. And this has helped me to
uncover some secrets and tricks that these ancient
enzymes use to carry out their diverse functions. But I’m not content
with just understanding how these enzymes function. I’m really interested in
how they got their functions in the first place. So an RNA molecule
is, essentially, a string of building
blocks called nucleotides arranged
in a certain sequence, just like words are
made of letters. So just like changing
letters can create words with new meanings, changing
nucleotides in an RNA sequence can create enzymes
with new functions. And this can happen
through multiple routes. Successful routes are those
that generate meaningful words– or functional enzymes– at each step of this process. So by reconstructing
these routes, I have discovered that
intermediate enzymes that show two functions
instead of one are key to the evolution
of enzyme function. These bifunctional
intermediates gradually let go of their
existing function and settle into their
newly acquired one. Now, imagine you have to go
to O’Hare from Hyde Park, and there is no
direct train route. So we start at Garfield
Red, get off at Jackson Red, transfer to Jackson Blue,
and then take the Blue Line all the way to O’Hare. This is possible
only because Jackson houses both red and blue lines. My research has
uncovered several of these Jackson-like nodes
in the evolutionary network that Connects diverse
enzyme functions. So this enables RNA enzymes
to seamlessly transition from one function to
the other, thereby producing this wide-ranging
capacity to sustain life. Understanding how the very
first enzymes looked and behaved will bring us closer
to understanding the chemistry of early life. And I think RNA could have
very well been the hands that rocked the cradle of baby life. Thank you very much. [APPLAUSE]

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