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Visualizing Cellular Messengers

Visualizing Cellular Messengers

Tuesday, September 29, 2015

The New York Academy of Sciences

Presented By

 

The development of increasingly sophisticated molecular probes and biosensors has had a major impact on our ability to visualize key players in signal transduction. This enables scientists to interrogate the complex interactions between second messengers, proteins, nucleic acids, metabolites and other biomolecules within a living cell in the context of physiological and pathological processes. This symposium offers a venue for discussion of state of the art chemical tools and imaging strategies for metal ions, redox signaling species and metabolites in the cell, as well as recent advances in the development of cellular delivery and targeting approaches and their application in the study of life processes ranging from neurotransmission to cancer.

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Nonmember (Student / Postdoc / Resident / Fellow)$30

 


The Chemical Biology Discussion Group is proudly supported by   American Chemical Society

Agenda

* Presentation titles and times are subject to change.


September 29, 2015

12:00 PM

Registration and Poster Set-up

12:30 PM

Welcome and Introduction
Sonya Dougal, PhD, The New York Academy of Sciences
Daniela Buccella, PhD, New York University

12:40 PM

Fluorescent Tools for Shedding Light on Cellular Magnesium
Daniela Buccella, PhD, New York University

1:15 PM

Loss of β-1,4- Branched N-Glycans Contributes to mir-424-Mediated Cell Cycle Arrest
Christopher Vaiana, MS, New York University

1:35 PM

Coffee Break and Poster Session

2:20 PM

Precise Redox Responses Imprinted by On-Demand Redox Targeting
Marcus Long, PhD, Cornell University

2:40 PM

Imaging Cellular Messengers with Genetically Encoded Sensors Composed of RNA
Samie Jaffrey, PhD, Weill Cornell Medical Center

3:15 PM

Development of Fluorescent Tools for Live Cell Imaging: Exploring the Possibility of Zinc Ions to Act as Cellular Messengers
Amy Palmer, PhD, University of Colorado

4:00 PM

Networking Reception and Poster Session

5:00 PM

Close

Speakers

Organizers

Daniela Buccella, PhD

New York University

Daniela Buccella was born in Caracas, Venezuela and received her B.S. degree in Chemistry from Universidad Simón Bolívar in 2002. She performed undergraduate research in the Venezuelan Institute for Scientific Research, working under the supervision of Prof. Roberto Sánchez-Delgado. She then moved to New York to conduct graduate studies at Columbia University working with Prof. Ged Parkin in the area of inorganic synthesis and catalysis. After receiving her Ph.D. degree in 2008, Daniela went to the Massachusetts Institute of Technology to work as an NIH postdoctoral fellow in the laboratory of Prof. Stephen J. Lippard. She returned to New York City in the fall of 2011 as an Assistant Professor in the Department of Chemistry at New York University. Work in her research group focuses on the development of new molecular probes and imaging strategies for the study of cellular metal homeostasis and chromatin remodeling by metalloenzymes.

Sonya Dougal, PhD

The New York Academy of Sciences

Speakers

Daniela Buccella, PhD

New York University

Daniela Buccella was born in Caracas, Venezuela and received her B.S. degree in Chemistry from Universidad Simón Bolívar in 2002. She performed undergraduate research in the Venezuelan Institute for Scientific Research, working under the supervision of Prof. Roberto Sánchez-Delgado. She then moved to New York to conduct graduate studies at Columbia University working with Prof. Ged Parkin in the area of inorganic synthesis and catalysis. After receiving her Ph.D. degree in 2008, Daniela went to the Massachusetts Institute of Technology to work as an NIH postdoctoral fellow in the laboratory of Prof. Stephen J. Lippard. She returned to New York City in the fall of 2011 as an Assistant Professor in the Department of Chemistry at New York University. Work in her research group focuses on the development of new molecular probes and imaging strategies for the study of cellular metal homeostasis and chromatin remodeling by metalloenzymes.

Samie Jaffrey, MD, PhD

Weill Medical College of Cornell University

Dr. Samie Jaffrey is a Professor of Pharmacology at the Weill Medical College of Cornell University.  He received an M.D. and Ph.D. from Johns Hopkins School of Medicine where he also conducted postdoctoral work.  Dr. Jaffrey’s laboratory focuses on identifying novel RNA regulatory pathways the control protein expression in normal cellular function and in disease processes. His research uses novel imaging, sequencing, microfluidic, and chemical biology approaches to address these questions.

Dr. Jaffrey’s laboratory developed a novel class of RNAs referred to as “RNA mimics of green fluorescent protein,” which are used to image RNA localization and monitor RNA processing in living cells.  This work has been recognized by the “Faculty of 1000” as one of its “all-time” top 10 ranked papers.  The Jaffrey laboratory extended this technology to create a new class of genetically encoded biosensors composed of RNA that allows signaling molecules to be imaged in living cells.

Dr. Jaffrey’s is the recipient of the Klingenstein Neuroscience Fellowship, Irma T. Hirschl Scholar award, the McKnight Foundation Technology development award, NIH EUREKA award, the NIH Director’s Transformative R01 award, the 2013 Blavatnik Award for Young Scientists, and the 2014 American Society for Biochemistry and Molecular Biology Young Investigator Award.

Marcus Long, PhD

Cornell University

Long was born in a small village in East Yorkshire, UK. He read chemistry as an undergraduate at Oxford University and worked there as researcher for one and a half years after graduation, studying asymmetric chemical transformations. He moved to Brandeis University to study biochemistry/enzymology in the lab of Prof Liz Hedstrom for his PhD. There he synthesized chemical tools that he showed could manipulate ubiquitin pathways. He thus became interested in cellular “mind control” by altering signaling pathways. He now works on studying the ramifications of redox signaling and new target discovery using targetable reactive electrophiles and oxidants in Yimon Aye’s lab.

Amy E. Palmer, PhD

University of Colorado

Amy E. Palmer received her B.A. cum laude in 1994 from Dartmouth College where she worked with Karen E. Wetterhahn on the toxicity of chromium compounds. She received her PhD in 2001 in Chemistry from Stanford University, under the direction of Edward I. Solomon. Her PhD work utilized spectroscopic methods to characterize the electronic and geometric structure and function of multi-copper oxidases. While obtaining her PhD, she also obtained a Masters degree in Science Education from Stanford University. From 2001-2005, Dr. Palmer was an NIH-postdoctoral fellow in the lab of Nobel laureate Roger Y. Tsien at the University of California San Diego. During this time she developed a family of genetically encoded fluorescent calcium sensors and used them to examine localized calcium signaling in mammalian cells. From 2005-2012 she was an Assistant Professor of Chemistry and Biochemistry at the University of Colorado-Boulder and a member of the BioFrontiers Institute. She was promoted to Associate Professor in 2012. In 2013 she was a visiting scientist at the Pasteur Institute in Paris, France where she studied Listeria pathogenesis. Her research focuses on developing fluorescent sensors for metal ions to probe metal distribution and dynamics in living cells, developing fluorescent tools for imaging host-pathogen interactions, and developing optically integrated microfluidics to characterize and optimize fluorescent probes. Professor Palmer is also passionate about teaching and overhauled undergraduate Physical Chemistry before tackling curriculum reform for General Chemistry. Professor Palmer is the recipient of a Sloan Foundation Research Fellowship (2010, Chemistry), NSF CAREER award (2010), Ed Stiefel Young Investigator Award in Biological Inorganic Chemistry (2010), NIH Director’s Pioneer Award (2014), and was the co-Chair of the Cell Biology of Metals Gordon Research Conference (2015).

Christopher Vaiana

New York University

Christopher Vaiana is a senior graduate student working in the laboratory of Dr. Lara Mahal, Department of Chemistry, New York University, focusing on the identification of biological roles of glycosylation patterns and their associated glycosyltransferase enzymes, using microRNA as a prediction tool.  Chris was born and raised in New York City, where he attended Archbishop Molloy High School in Queens.  In 2007 he received a B.A. in Biology from SUNY Binghamton.  As an undergraduate he conducted research in the lab of C.J. Zhong, focusing on tunable gold nanoparticle aggregation.  Following college, Chris served four years active duty military as a Lieutenant in the Air Force Research Laboratory, Wright Patterson Air Force Base, Dayton OH, where he worked under Dr. Rajesh Naik designing biologically-functionalized materials for aerospace applications.  Concurrently, he earned a M.S. in Biochemistry from Wright State University under the advice of Dr. Madhavi Kadakia, where he studied EGF-functionalized montmorillonite for wound healing applications.  Chris is the recipient of the Military Officer of the Year Award (2009, Materials & Manufacturing Directorate, Air Force Research Lab), the Graduate Student of the Year Award (2010, Wright State University), and the Outstanding Teaching Award (2015, New York University CAS).

Sponsors

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Tri-Institutional PhD Program in Chemical Biology

The Chemical Biology Discussion Group is proudly supported by   American Chemical Society

Abstracts

Imaging Cellular Messengers with Genetically Encoded Sensors Composed of RNA
Samie R. Jaffrey, MD, PhD, Department of Pharmacology, Weill Medical College, Cornell University

Genetically encoded sensors are powerful tools for imaging intracellular metabolites and signaling molecules. However, developing sensors is challenging because they require proteins that undergo conformational changes upon binding the desired target molecule. We describe an approach for generating fluorescent sensors based on Spinach, an RNA sequence that binds and activates the fluorescence of a small-molecule fluorophore. We have developed a variety of versatile approaches for linking metabolite-binding RNAs to Spinach so that metabolite levels directly induce Spinach fluorescence in cells.  We show that these sensors can detect a variety of different small molecules in vitro and in living cells. These RNAs constitute a versatile approach for fluorescence imaging of small molecules and have the potential to detect essentially any cellular biomolecule.
 

Fluorescent Tools for Shedding Light on Cellular Magnesium
Daniela Buccella, PhD

Magnesium is the most abundant divalent cation in mammalian cells, with multiple roles that are essential for cellular function. Disrupted homeostasis of this metal has been associated with numerous pathologies including age-related diseases, neurodegeneration, and cancer. However, detailed understanding of the mechanisms by which intracellular Mg2+ concentrations are regulated and their role in human health is still lacking, hampered by the paucity in efficient tools for the detection of the ion in the complex environment of the cell. Fluorescence imaging has emerged as the most promising tool to study intracellular cations, but current commercially available fluorescent indicators do not offer the combination of selectivity and spatial resolution required to elucidate many unanswered questions about cellular magnesium homeostasis. This lecture will recount our efforts toward the development of molecular probes for the study of Mg2+ by live-cell microscopy techniques, seeking to shed light on fundamental aspects of magnesium biology. We have developed new fluorescent indicators that exhibit improved selectivity and subcellular resolution, which have enabled the study of magnesium dynamics in mitochondria and the uncovering of Mg2+ fluctuations in early stages of apoptosis. Furthermore, our studies have revealed that complex binding schemes leading to formation of ternary complexes may cause common indicators to co-report on various intracellular species, challenging the interpretation of fluorescent imaging experiments. In light of these results, new approaches for the study of metal speciation in the cell will be discussed.
 
Coauthors: Mohammad S. Afzal, BS1, Jessica J. Gruskos, BS1, Qitian Lin, BS1, Brismar Pinto-Pacheco, BS1, Sarina C. Schwartz, MSc1, Guangqian Zhang, MSc1
 
1. Department of Chemistry, New York University, New York, New York, USA
 

Development of Fluorescent Tools for Live Cell Imaging: Exploring the Possibility of Zinc Ions to Act as Cellular Messengers
Amy E Palmer, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado Boulder

Our research lies at the interface of chemistry and biology, where the application of chemical and physical principles provides a unique opportunity to better understand the fundamental biochemistry of living cells. Cells are complex entities that must integrate internal and external signals in order to coordinate diverse functions. Living cells are also dynamic, and this dynamism is key to understanding the mechanisms between cause and effect for biological processes. Our lab develops new technologies to interrogate signaling cascades in cells to understand how the actions of specific proteins, molecules, and ions contribute to cellular function. We combine in vitro spectroscopic and biophysical techniques with protein design and engineering to develop novel fluorescent probes, and use long-term time-lapse fluorescence microscopy to elucidate the mechanisms of cellular signaling pathways. We are specifically interested in how cells regulate metal ions. Emerging evidence suggests that zinc can be mobilized from labile pools within cells in response to cellular cues, representing an exciting new paradigm for exploring how mammalian cells control zinc and how zinc influences cellular function.  This talk will highlight our efforts to develop genetically encoded FRET-based sensors for quantitative mapping of zinc ions in cells, and studies that explore the downstream targets of zinc.
 

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