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our guest speaker will be
Michael Hecht, PhD
Princeton University
Department of Chemistry
“Synthetic
Biology: From Protein Design Toward Artificial Genomes”
Date: Wednesday,
February 24, 2010
Lecture at 6:00 p.m.
Frick Laboratory, Room 120
Princeton University*
Dinner following at
Kalluri Corner Restaurant
Princeton University Map
Driving Directions
Abstract
The entire collection of
genes and proteins in all the organisms on earth represents
a minuscule fraction of the sequences that - in principle -
could encode biological activity. From the enormous
diversity of theoretically possible sequences, evolution has
selected a very small collection of ‘parts’ to sustain
living cells (only ~4,000 genes in E. coli and ~20,000 in
humans.) These considerations might lead to the supposition
that genes and proteins capable of sustaining life are
somehow ‘special.’ Is this true? Or can one produce
biologically functional macromolecules from artificial
sequences that are not derived from nature, but designed in
the laboratory entirely ‘from scratch’?
To address these
questions, we designed a collection of >1,000,000 de novo
proteins (a model ‘proteome’) encoded by a library of
synthetic genes (an artificial ‘genome’). The capacity of
these artificial parts to encode biological functions was
tested by transforming the collection of sequences into
strains of E. coli deleted for functions that are required
for growth under selective conditions. Surprisingly, several
auxotrophs of E. coli were rescued, thereby demonstrating
that novel sequences bearing little or no similarity to
natural sequences can provide essential biological
activities. Moreover, co-expression of several de novo
sequences compensates for the simultaneous deletion of
several natural genes.
This initial small-scale
foray into artificial genomics suggests that (i) the toolkit
for biology need not be limited to genes and proteins
already existing in nature; and (ii) the construction of
entirely artificial genomes capable of sustaining life may
soon be within reach.
Biography
Michael Hecht grew up in
midtown Manhattan. He received his BA summa cum laude in
Chemistry from Cornell University, where he worked with Prof.
Harold Scheraga. He earned his PhD in Biology from MIT, where he
was Prof. Robert Sauer’s first graduate student. Hecht then did
post-doctoral research with Profs. David and Jane Richardson in
the Biochemistry Department at Duke University Medical School.
In 1990, Hecht joined the faculty at Princeton University, where
is a Professor of Chemistry and holds an affiliated appointment
in Molecular Biology. At Princeton, he has served as the
Director of Undergraduate Studies, and as the Associate Chair of
the Chemistry Department. He has taught courses ranging from
Introductory Chemistry, to graduate seminars on protein folding
and design.
Hecht’s research group works
at the interface of chemistry and biology, with current research
focused in two areas: The first deals with the molecular
determinants of Alzheimer’s disease and the search for
anti-Alzheimer’s therapeutics. The second area of research
focuses on Synthetic Biology, and includes projects ranging from
the design of novel proteins to the construction of artificial
genomes.
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