From: Alice Ting (ating$##$mit.edu)
Date: Fri Apr 05 2002 - 13:17:06 EST
Post-Doctoral Position
Design and Synthesis of New Molecules for Detecting and Manipulating
Cellular Signals
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, MA, USA
A unique opportunity exists for a skilled organic chemist to work with a
vibrant collaborative team led by Professor Alice Y. Ting to design,
synthesize, and apply new molecules towards the detection and manipulation
of intracellular biochemical signals. The overall goal of the research
program is to understand how living cells process information and
orchestrate appropriate responses. There is the possibility of joining one
of two project areas:
1. Site-Specific Incorporation of Novel Chemical Probes into Recombinant
Proteins in Living Cells: To track protein localization, activity,
interaction partners or conformational changes as components of cellular
signaling pathways, biologists need general tools for the in vivo
site-specific labeling of proteins with fluorophores, spin labels,
photoactivatable cross-linkers, radiolabels, metal-binding ligands, and
other useful small-molecule probes. Traditional chemical labeling methods,
such as cysteine-maleimide conjugation, are too promiscuous for in vivo
use, and the most widely used genetic method, fusion to green fluorescent
protein (GFP), carries a payload of 238 amino acids and can only be
visualized by fluorescence. We propose to use organic synthesis in
combination with enzyme engineering to develop reagents for the
site-specific labeling of any desired protein in vivo. These reagents
should then allow the productive study of signaling events within the
native cellular context, while also providing the opportunity to influence
and control cellular behavior through attachment of novel chemical
functionalities to specific protein targets.
2. Cell-Based Gene Expression Profiling: Genomic biology has motivated the
search for new general techniques for detecting gene expression in living
cells. Existing methods, such as fusion to reporter genes, are sterically
perturbative and insufficiently sensitive for detection of small or
transient changes in gene expression. We propose to develop the next
generation of gene expression reporters, capable of detecting endogenous,
unaltered genes with extremely high sensitivity and reproducibility. The
new methodology will be based on engineered allosteric ribozymes that act
on designed small-molecule substrates. We expect the methodology to be
sufficiently general for eventual extension to genome-wide cell-based
expression profiling
In addition to drawing from organic synthesis, exposure to a range of
biochemical and cell biological techniques is envisaged, including protein
and RNA evolution, live cell fluorescence imaging, and mammalian cell
culture. There will be the opportunity to interact with scientists from a
variety of disciplines spanning physical chemistry, chemical engineering,
and biology. The position will be available starting July 1, 2002. Please
see: http://web.mit.edu/chemistry/Ting_Lab for more information. Please
email CV, research summary, and at least three letters of recommendation to
ating$##$mit.edu or send hard copies to the temporary address below:
Professor Alice Y. Ting
Department of Chemistry and Biochemistry
University of California at San Diego
310 Cellular & Molecular Medicine West
9500 Gilman Drive
La Jolla, CA 92093-0647
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