General

Special Biological Chemistry Seminar, Vinayak Argarwal, The University of California San Diego

Mon, 2016-01-11 13:00 - 14:00
Location: 

Carolyn Hoff Lynch Room

For inquiries contact Camille Pride at campride@sas.upenn.edu

 

Title: Understanding natural product biosynthetic routes for polybrominated pollutants and toxins in the marine environment

 

Abstract:

The marine environment provides a plenitude of naturally produced organic pollutants and toxins. Of these, polybrominated marine natural products, such as endocrine disrupting polybrominated diphenyl ethers, dioxins, and pyrroles, biomagnify in the marine food web and are available to be passed onto humans via seafood. Despite their recognized toxic potential, routes for the production of these polybrominated molecules in the marine metabolome have not been elucidated. This in turn hinders the development of diagnostic tools to discover and query the biosynthetic potential of other natural sources that introduce these polybrominated pollutants into the environment.

The research presented in this seminar takes a fresh look at these molecules from a biochemists’ perspective, and uses an interdisciplinary (meta)genome mining direction to characterize the biosynthetic routes of polybrominated pollutants and toxins. Based on a 'predictive retrobiosynthetic' approach, biosynthetic hypotheses are advanced that are then rigorously tested using a combination of genetic and biochemical experiments. Complemented by mass spectrometry and other analytical techniques, data generated during the course of this study will be used to drive the discovery of under-appreciated additional natural sources that are contributing to the human and environmental exposure to these naturally produced polybrominated pollutants. Furthermore, the research design recognizes and seeks to exploit the numerous opportunities that will present themselves for the advancement of halogenation enzymology and novel marine biochemistry.

Special Biological Chemistry Seminar, Gregory Alushin, National Heart, Lung, and Blood Institute, NIH

Thu, 2016-01-07 13:00 - 14:00
Location: 

Carolyn Hoff Lynch Room

For inquiries contact Camille Pride at campride@sas.upenn.edu

 

Title: Cytoskeletal structural plasticity in force generation and mechanosensation

 

Abstract:

Cytoskeletal filaments play a central role in the generation and transmission forces essential to fundamental biological processes including cell division, differentiation, and morphogenesis, and their dysfunction in disease states such as cancer. Utilizing structural studies with cryo-electron microscopy and complimentary biophysical / cell biological approaches, we aim to uncover the detailed mechanisms of the macromolecular interactions which orchestrate these events. At the molecular level, they are driven by conformational changes in the component proteins of these filaments, tubulin and actin, as well as their binding partners. I will discuss my previous studies of the GTP hydrolysis-dependent conformational cycle underlying microtubule dynamic instability, which is critical for generating forces to segregate chromosomes during mitosis and is the target of several chemotherapeutic drugs. I will then focus on our ongoing efforts to visualize conformational changes in actin filaments and closely associated binding partners key for both generating forces (myosin motor proteins) and sensing forces (adhesion proteins and, provocatively, actin filaments themselves) to facilitate mechanotransduction. By dissecting the detailed molecular mechanisms of mechanosensation pathways, our long-term aim is to develop novel targets for therapeutic intervention in cancer metastasis and regenerative medicine.

Special Biological Chemistry Seminar, Ralph Kleiner, The Rockefeller University

Mon, 2015-12-21 13:00 - 14:00
Location: 

Carolyn Hoff Lynch Room

For inquiries contact Camille Pride at campride@sas.upenn.edu 

 

Title:   Chemical Approaches to Illuminate Cellular Mechanisms Ensuring Genome Stability

 

Abstract:

The maintenance of genome stability is a major challenge faced by cells and errors in this process can lead to developmental defects and diseases such as cancer. In this seminar, I will describe the development and application of chemical tools to investigate fundamental molecular mechanisms ensuring genome stability. Using a chemical proteomics approach, we profiled, in native proteomes, direct binders of the phosphorylated histone variant, gH2AX, a central mediator of DNA double-strand break repair. These studies led to the identification of proteins that ‘read’ gH2AX, including the DNA repair protein, 53BP1, whose localization at chromosomal DNA breaks was shown to involve direct recognition of this phospho-‘mark’. I will also highlight progress towards profiling histone-mediated interactions in living cells involved in accurate chromosome segregation. This work shows how recognition of specific chemical epitopes within chromatin contributes to essential mechanisms that maintain genome stability, and demonstrates the utility of chemical approaches for the discovery and characterization of macromolecular interactions occurring in the cellular context.

Special Biological Chemistry Seminar, Siddhesh Kamat, The Scripps Research Institute

Thu, 2015-12-17 13:00 - 14:00
Location: 

Carolyn Hoff Lynch Room 

Inquiries please contact Camille Pride at campride@sas.upenn.edu 

 

Title: A lipid signaling pathway that controls immune cell extravasation in a human neurological disease

 

Abstract: 

Understanding hereditary human disorders has benefited from DNA sequencing technologies, which have, to date, facilitated determination of the genetic basis for over 4,000 inherited diseases in humans. Assigning biochemical and cellular functions to the proteins encoded by these mutated genes is critical to achieve a deeper mechanistic understanding of human genetic disorders and for identifying potential treatment strategies for these diseases. Several hereditary nervous system diseases are caused by deleterious mutations in poorly characterized enzymes from the serine hydrolase class. PHARC (polyneuropathy, hearing loss, ataxia, retinal pigmentation, cataract) is one such neurological disease, caused by deleterious null mutations in the Abhd12 gene, which encodes the serine hydrolase ABHD12. The major symptoms of PHARC include polymodal sensorimotor defects linked to peripheral neuropathy, hearing loss, early onset of cataract and blindness, cerebellar atrophy and demyelination of sensorimotor neurons. The Cravatt lab determined using Abhd12–/– mice and lipidomics that ABHD12 serves as a major lysophosphatidylserine (lyso-PS) lipase in the mammalian brain, degrading lyso-PS to produce glycerophosphoserine (GPS) and free fatty acid (FFA). Recently we have identified and functionally annotated ABHD16A as the principal phosphatidylserine (PS) lipase in the mammalian central nervous system and the immune system, where it regulates immunomodulatory lyso-PS production. Our studies thus designate ABHD16A as a key enzyme that functions upstream of ABHD12, and that these enzymes together form a dynamic pathway for regulating lyso-PS signaling in vivo. Furthermore we have found that lyso-PS lipids are intricately involved in immune cell trafficking, and are in particular critical for the extravasation of T-cells into tissues. I will present our lipidomics and immunological findings in mouse genetic models that support the broader role for the ABHD16A-ABHD12-lyso-PS signaling network in (neuro)-immunology.

 

 

Special Biological Chemistry Seminar, Yael David, Princeton University

Fri, 2015-12-04 13:00 - 14:00
Location: 

Carolyn Hoff Lynch Room

Inquires please contact Camille Pride at campride@sas.upenn.edu

 

Title:    Chemistry on Chromatin: Modifying Histones In Vivo Using Protein Trans-Splicing

Schelter Group Wins Postdoctoral Fellowship

Associate Professor Eric Schelter has been awarded a Postdoctoral Program in Environmental Chemistry from the Dreyfus Foundation. The award provides a principal investigator with a two year fellowship to appoint a Postdoctoral Fellow to perform fundamental research in the chemical sciences or engineering related to the environment. More information on the program can be found here.

Zahra Fakhraai Research Featured

Assistant Professor Zahra Fakhraai is part of an interdisciplinary team that received a five-year, $3.6 million grant from the National Science Foundation to develop materials for multifunctional coatings on emergency tents, enabling them to manage water, prevent the spread of bacteria and capture and store solar energy.

 

Organic Chemistry Seminar (Andy Peat, GlaxoSmithKline)

Mon, 2016-02-08 12:00 - 13:00
Location: 

Lynch Lecture Hall Chemistry Complex

Inquires please contact Camille Pride at campride@sas.upenn.edu

 

Inorganic Chemistry Seminar (Kirill Kovnir, University of California, Davis)

Tue, 2016-01-26 12:00 - 13:00
Location: 

Lynch Lecture Hall

Chemistry Complex

Inquires please contact Camille Pride at campride@sas.upenn.edu

 

Inorganic Chemistry Seminar (Vlad M. Iluc, University of Notre Dame)

Tue, 2016-04-19 12:00 - 13:00
Location: 
Lynch Lecture Hall Chemistry Complex

Inquires please contact Camille Pride at campride@sas.upenn.edu

Department of Chemistry

231 S. 34 Street, Philadelphia, PA 19104-6323

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