A Systems Approach to Studying Host-Pathogen Relationships

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A Systems Approach to Studying Host-Pathogen Relationships

Tuesday, March 16, 2010

The New York Academy of Sciences

Presented By

 

This symposium will bring together researchers who use the tools of Systems Biology, along with genome analysis and bioinformatics, to better understand the complex relationships between host and pathogen, including the immune response.

Agenda

Antiviral Response Dictated by Choreographed Cascade of Transcription Factors
Steve Kleinstein, Yale University

A Stated Strategy for Pathogen Discovery
Gustavo Palacios, Mailman School of Public Health - Columbia University

Swine, avian and human influenza and the origins of influenza A (H1N1) pandemic strain
Raul Rabadan, Columbia University College of Physicians and Surgeons

Networking reception to follow

Speakers

Organizers

Andrea Califano

Columbia University

Aris Economides

Regeneron Pharmaceuticals

Gustavo Stolovitzky

IBM

Speakers

Steve Kleinstein

Yale University

Steven H. Kleinstein received his Ph.D. in Computer Science from Princeton University in 2002. He is currently an Assistant Professor in the Department of Pathology at the Yale University School of Medicine, were he is part of the Pathology Informatics division and the Yale Center for Medical Informatics. Dr. Kleinstein has over 15 years of experience in computational biology and is an expert in the field of computational immunology, where his work combines techniques from dynamic modeling, systems biology and bioinformatics to better understand the immune response.

Gustavo Palacios

Mailman School of Public Health - Columbia University

Gustavo Palacios is an Assistant Professor of Clinical Epidemiology in the Center for Infection and Immunity (CII) at Columbia University. A graduate of the Universidad de Buenos Aires, he worked in virus diagnostics and molecular epidemiology at the Argentinian National Institute of Infectious Diseases prior to joining the CII as a postdoctoral fellow in 2002. Dr. Palacios' research is focused on microbial diagnostics and discovery. He has contributed to the development of MassTag PCR as a tool for syndromic surveilance and virus diagnostics, the invention of the first panmicrobial microarray; the use of deep sequencing in pathogen discovery and the discovery of more than 50 viruses including rhinovirus C, Dandenong virus, and LuJo virus.

Raul Rabadan

Columbia University College of Physicians and Surgeons

Raul Rabadan is an Assistant Professor in the Department of Biomedical Informatics and in the Center for Computational Biology and Bioinformatics, at the Columbia University College of Physicians and Surgeons. Dr. Rabadan has been the Martin A. and Helen Chooljian Member at The Simons Center for Systems Biology at the Institute for Advanced Study in Princeton, New Jersey. From 2001 to 2003 he was a fellow at the Theoretical Physics Division at CERN, the European Organization for Nuclear Research, in Geneva, Switzerland. In 2003 he joined the Physics Group of the School of Natural Sciences at the Institute for Advanced Study. Dr. Rabadan’s current interest focuses on patterns of evolution in biological systems, in particular, RNA viruses.

Abstracts

Antiviral Response Dictated by Choreographed Cascade of Transcription Factors

Steve Kleinstein, Yale University

The dendritic cell (DC) is a master regulator of immune responses. Pathogenic viruses subvert normal immune function in DCs through the expression of immune antagonists. Understanding how these antagonists interact with the host immune system requires knowledge of the underlying genetic regulatory network that operates during an uninhibited antiviral response. To isolate and identify this network, we studied DCs infected with Newcastle disease virus, which is able to stimulate innate immunity and DC maturation, but lacks the ability to evade the human interferon response. To analyze this experimental model, we developed a new approach integrating genome-wide expression kinetics and time-dependent promoter analysis. Our approach infers the transcription factors driving gene expression changes, determines the timing of their activity and identifies a causal chain of regulation. In addition to effectively recapitulating current biological knowledge, we predicted, and validated experimentally, antiviral roles for several novel transcription factors. More generally, our results show how a genetic program can be temporally controlled through a single regulatory network to achieve the large-scale genetic reprogramming characteristic of cell-state transitions.

A Stated Strategy for Pathogen Discovery

Gustavo Palacios, Mailman School of Public Health - Columbia University

Recent advances in nucleic acid diagnostic technologies have revolutionized microbiology by facilitating rapid, sensitive pathogen surveillance and differential diagnosis of infectious diseases. With the expansion and dissemination of genomic sequencing technology we are discovering new microbes at an accelerating pace. We will discuss the strengths and limitations of various assay platforms and describe a staged strategy for Pathogen Discovery. We will also discuss the challenges in proving a causal relationship between the presence of a candidate organism and disease. Sample preparation remains one of the more important challenges in the field. To illustrate the complexity of pursuing pathogen discovery research, we will include examples from our work that are intended to provide insights into the process that led to the selection of particular strategies.

Swine, avian and human influenza and the origins of influenza A (H1N1) pandemic strain

Raul Rabadan, Columbia University College of Physicians and Surgeons

Evolution is a dynamical process that shape the genomes of viruses and their hosts. We will talk about patterns in mutations and reassortments, selection and pathogenesis, in the context of the recent influenza A (H1N1) pandemic strain.

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