Research Opportunities in the Jaffrey LabSeveral types of positions are currently available:
Chemical Biology and Biochemistry Postdoctoral Positions
Our laboratory has recently described new “RNA mimics” of
green fluorescent protein. These
RNA aptamer sequences bind fluorophores that resemble the fluorophore in GFP,
and switch them from a nonfluorescent state to a fluorescent state. We have developed a series of RNAs that
bind GFP-related fluorophores and produce a palette of fluorescence emissions
from blue to red. This work was
recently described in a paper in Science (Paige, J.S., Wu, K.Y., Jaffrey, S.R.
RNA mimics of green fluorescent protein, Science, 333:642-646, 2011.)
Much of our work is focused on “Spinach,” an RNA that emits
a bright green fluorescence. We have tagged noncoding RNAs with Spinach,
expressed these RNAs, and imaged them in living cells. These experiments have
resulted in powerful and unprecedented insights into RNA trafficking in cells.
We are also developing new, brighter RNA-fluorophore
complexes. For example we have developed “Carrot” and “Radish” RNA aptamers
which bind fluorophores similar to the red fluorescent protein fluorophore, and
which provide bright orange and red fluorescence. We are currently optimizing
new techniques for multiplexed imaging of RNA in cells.
We are also working on converting these RNA-fluorophore
complexes into novel genetically encoded sensors. For example, we have
developed an allosteric RNA device that binds ATP, inducing a conformational
change which leads to marked fluorescence enhancement of Spinach. When these
RNA devices are expressed in cells, we can readily detect how the levels of
specific metabolites change over time. Since RNA aptamers can easily be
generated against any protein or small molecule, we can conceivably create
novel RNA sensors that can detect any molecule. We expect that these genetically encoded RNA-based sensors
will form the foundation for a fundamentally novel technology that will rival
or replace current FRET-based approaches.
We want creative and ambitious postdocs who are interested
in projects that further develop and apply this novel and innovative
technology. For instance, we are
developing RNA-fluorophore complexes with new photophysical properties,
including photobleaching and photoactivation. We are also developing DNA
aptamers which mimic GFP. We are
developing new RNA sensor microarrays to potentially detect dozens or hundreds
of small molecules in a tissue sample at once. We are also using Spinach to
image fundamental molecular biology reactions, such as splicing, enabling RNA
processing events to be monitored in living cells. Additionally, we are
interested in using Spinach and Carrot to image the trafficking of novel
non-coding RNA in cells in order to uncover their biological functions. These and a variety of other projects
are currently a major focus of the laboratory.
Neuroscience, Cell Biology, and Signaling Postdoctoral PositionsWe are currently seeking creative and motivated postdoctoral candidates who are fascinated by the development of the nervous system and the remarkable cell biology of neurons.
One major focus of our laboratory is to understand the
process of “local translation,” which is the synthesis of proteins within
axons, typically in response to various extracellular cues. We have identified
mRNAs that are present in growth cones, and provided the first evidence for a
specific mRNA that is required within axons for axonal guidance. Subsequent
studies from our group identified novel signaling proteins that are synthesized
in axons during axon guidance processes. Also, we have found that locally
translated proteins are locally degraded through the ubiquitin-proteasome
system. We have developed novel
viral tools and microfluidic strategies for studying axonal signaling and local
translation, as well as proteomic methodologies for studying important
signaling mechanisms in axons. For
examples of our work, see Wu et al., Nature, 436:1020-4, 2005; Hengst et al.,
Nature Cell Biology, 11:1024-30, 2009; Xu et al., Nature Biotechnology,
28:868-873, 2010).
Another goal of our laboratory is to understand the axonal
signaling pathways that lead to axon degeneration. Axon degeneration occurs during axonal pruning, a process
that is critical for refinement of neuronal connectivity during brain
development. Axon degeneration is
also a prominent feature of several neurodegenerative diseases, such as
multiple sclerosis and Parkinson’s disease, which may involve the aberrant
activation of pathways that are typically used during developmental axon
pruning. As described below, we
have identified a novel signaling pathway that controls the onset of axon
degeneration.
We have several projects available for future postdocs in
our dynamic and interactive group:
Project 1: Axon guidance pathways controlled by mRNA
polyadenylation and degradation in axons
Although numerous signaling molecules, such as axon guidance
cues and trophic factors, induce mRNA translation in axons and growth cones, it
is unknown how receptor activation is coupled to mRNA translation. One mechanism to induce mRNA
translation is to induce its polyadenylation, the process that generates polyA
tails on mRNAs. Many neuronal
mRNAs are translationally silent since they lack polyA tails, and
polyadenylation is expected to convert them to translationally competent
transcripts. However, whether polyadenylation
occurs in axons, and whether it regulates local translation is unclear. We have identified a novel
axon-enriched polyA polymerase, which appears to mediate receptor-activated
polyadenylation. This project
involves characterizing the targets of this axon-enriched polyA polymerase and
determining the role of this novel enzyme in local translation and axon
pathfinding. This project will
fundamentally alter our understanding of mRNA translation in axons by
characterizing an enzyme that is likely to have a critical role in the
regulation of local translation.
Project 2:
Defining the axonal pruning and degeneration pathway
During neurodevelopment, axons undergo “pruning” in which
excess axonal branches are eliminated.
The process of axon pruning appears to involve pathways that are
aberrantly activated in various neurodegenerative diseases. Therefore, understanding how axons
undergo degeneration has implications for both neurodevelopment and neurodegeneration. We have identified novel signaling
proteins that are activated during these pathways, some of which are regulated
by NAD, a metabolic cofactor widely known for its roles in redox biology. Our work suggests a novel link between
mitochondria, the cytoskeleton, and axon pruning and degeneration. Unlike apoptotic pathways, which are
well described, the signaling pathway that leads to axon degeneration is poorly
understood and a major unresolved question in neuroscience. The major goal of this project is to
define this novel and highly important signaling pathway that mediates axon
pruning and degeneration.
These positions provide the opportunity for considerable
creativity and innovation and applicants with these skills are also especially
encouraged to apply. The wide
range of research topics in the Jaffrey lab makes it an excellent environment
for interdisciplinary training.
The laboratory environment is highly collegial and interactive, so
excellent written and oral communication skills are a must.
Cornell University's Weill Medical College is located in
Manhattan's Upper East Side, immediately adjacent to the Sloan Kettering
Institute and Rockefeller University. This "tri-institutional campus"
includes several hundred principal investigators and postdocs, and has one of the
highest densities of biomedical scientists in the world. This rich scientific
environment provides unique and unparalleled research training opportunities,
including research seminars given by leaders in science from throughout the
U.S. and abroad, opportunities for collaborations, exposure to diverse research
programs, and highly sophisticated core facilities.
Questions about this position and/or applications,
comprising a CV, statement of research interests, and contact information for
three references, should be e-mailed to Dr. Samie Jaffrey at jaffreylab2 at
gmail.com. A hard copy of the
application is not required.
Graduate StudentsThe Jaffrey lab is open to graduate students with diverse interests, including Neuroscience, Pharmacology, Cell Biology, Chemistry, Genetics, and Developmental Biology. Recent rotation students include those enrolled in the Tri-Institutional Chemical Biology Program, Computational Biology Program, and MD/PhD program.
Interested students should e-mail Samie Jaffrey to arrange a rotation.