Positions in (1) Chemical Biology; (2) Molecular Biology; and (3) Molecular Neuroscience are available:

(1) Chemical Biology and Fluorescence Imaging Postdoctoral Positions:

A major goal in RNA research is to image RNA and its movements in living cells. RNA imaging provides insights into the functions of RNA and is carefully regulated during cell signaling and cell division. However, RNA imaging is technically challenging.

We recently described “RNA mimics” of green fluorescent protein. These are RNA aptamer sequences that bind fluorophores that resemble the fluorophore in GFP, and switch on their fluorescence. We developed RNAs that bind a series of GFP-related fluorophores, producing a palette of fluorescence emissions ranging from blue to red. For example, “Spinach,” is an RNA that emits a bright green fluorescence. We have tagged noncoding RNAs with Spinach, expressed these RNAs, and imaged them in living cells.

We also developed a novel platform for imaging metabolites in live cells. Genetically encoded sensors are usually composed of proteins, and are limited since proteins cannot be easily designed to bind to any arbitrary target of interest. To overcome this problem, we developed biosensors composed of RNA. This approach takes advantage of the ease of generating RNA aptamers that can bind virtually any target molecule. We fuse these aptamers to Spinach so that when the target molecule binds the aptamer, it allosterically induces the fluorescence of Spinach. These RNAs can detect the dynamics in metabolite levels in living cells in real time. We expect that these genetically encoded RNA-based sensors will rival or replace current FRET-based approaches.

This work was described in two papers in Science and two papers in Nature Methods. See www.jaffreylab.org for more details.

Current projects include developing new, brighter RNA-fluorophore complexes. For example we have developed “Carrot” and “Radish” RNA aptamers that bind fluorophores similar to the red fluorescent protein fluorophore, and exhibit bright orange and red fluorescence. We are developing RNA-fluorophore complexes with new photophysical properties, including resistance to photobleaching and photoactivation. We are also using Spinach to image molecular biology reactions, such as splicing, enabling RNA processing events to be imaged in living cells. Additionally, we are using Spinach and Carrot to uncover the biological functions of diverse noncoding RNAs.

For our sensor work, we are developing new RNA sensor microarrays to detect dozens or hundreds of small molecules in a tissue sample at once. We are developing novel types of sensors to image modified proteins and the dynamics of epigenetic modifications in cells.

We have positions available for postdocs in projects that range from molecular biology, imaging, chemical biology, and synthetic chemistry. Postdoctoral candidates who have expertise in imaging, microscopy, fluorescence, fluorescent proteins, synthetic biology, RNA biochemistry, or related areas are welcome to apply. Postdocs who have experience with synthetic chemistry, especially related to fluorescent dye synthesis are also encouraged to apply.

(2) RNA Molecular Biology: N6-Methyladenosine Postdoctoral Positions

We recently discovered that mRNA contains a fifth base, N6-methyladenosine (m6A). Although m6A was detected in RNA nearly 40 years ago, it was never clear if m6A was found in mRNA. In 2012 we described a new next-generation sequencing approach, termed MeRIP-Seq, which showed that m6A is indeed a widespread base in mRNA. Thus, adenosine methylation impacts a substantial portion of the transcriptome.

m6A is predominantly found in either the 5’ regions of transcripts or near the stop codon. The highly selective localization of m6A in mRNAs suggests that m6A has an important role in regulating mRNA function.

Our work on m6A was described in papers in Cell and Nature Neuroscience.

Despite the high prevalence of m6A in mammalian mRNA, the function of this modified base is not known. We are uncovering the mechanism by which m6A influences the fate and function of mRNAs. Furthermore, we are exploring how signaling pathways regulate m6A levels in mRNAs, and how m6A regulates diverse physiological processes. We use molecular biology, sequencing, bioinformatic, and chemical biology approaches to explore this novel form of mRNA regulation.

Our projects related to m6A provide a unique opportunity to explore a completely new area of RNA molecular biology. Postdocs will have the opportunity to work on projects that will result in seminal papers that will provide the foundation for what will eventually become a major area of molecular biology research. Postdocs with expertise in molecular biology, especially pathways related to RNA (e.g. splicing, noncoding RNAs, transcription, etc) are encouraged to apply.

(3) Molecular Neuroscience and RNA Biology Postdoctoral Positions

Protein expression in synapses and axons is critical for synaptic plasticity, axon guidance, and for circuit formation. As a result, RNA-binding and RNA-regulatory proteins are often mutated in neurodevelopmental diseases.

Protein expression in synapses and axons is regulated by “local translation,” which is the synthesis of proteins directly within synapses and axons using localized ribosomes and mRNAs. We identified mRNAs that are present in growth cones, and were the first to show that specific mRNAs are required within axons for axonal guidance.

Recently we uncovered a novel form of regulation involving localized mRNA degradation. We showed that axons and dendritic spines are highly enriched in RNA degradation machinery and that signaling pathways can act to induce RNA degradation. Our findings suggest that a major mechanism to control protein expression is highly localized mRNA degradation, thereby limiting the repertoire of proteins that can by locally synthesized in axons.

Our work has been published in Cell, Nature, Neuron, Nature Cell Biology, and other journals.

Projects focus on understanding the function of RNA degradation proteins enriched in growth cones and synapses, and to determine how RNA degradation is regulated by synaptic signaling. We suspect that precise control of RNA degradation has major roles in synaptic plasticity and axon guidance. We have also found that noncoding RNAs are enriched in synapses and growth cones. Projects also focus on noncoding RNAs and their roles in synaptic function.

Postdocs with experience in neuroscience or molecular biology will be well-suited to explore projects in this area. Postdoc will have the opportunity to use 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

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The Jaffrey lab covers projects in diverse areas, including molecular biology, neuroscience, chemical biology, and imaging. Postdocs are exposed to research questions and techniques in the forefront of various fields. This type of training environment is exceptionally valuable for individuals who are interested in pursuing careers in academia or leadership positions in pharma.

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 scientific leaders from throughout the world, opportunities for collaborations, and highly sophisticated core facilities.

Members of the Jaffrey lab have received prestigious fellowships, including the Damon Runyon, Life Sciences, EMBO, and the NIH K99 Pathway to Independence award. Former postdocs have moved on to independent academic faculty positions throughout the US, China and Europe. Other laboratory members have moved on to leadership positions in Pharma.

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