Research Group

Ph.D. Candidates	Postdoctoral Associates
Song Li Usha Nandini Raghavan Ranran Zhang Assieh S. Moghaddam	Dr. Juilee Thakar
group alumni

Our goal is to develop close collaborations with strong experimental and theoretical components. By blending cross and inter-disciplinary expertise we hope to expand scientific inquiry in new and exciting directions. Here is a recent writeup on my research.

Current Research Support

• Congratulations to Dr. Juliee Thakar for securing a Postdoctoral Fellowship from the Cancer Research Institute

• USDA NRI 2006-02158, Guard cell ABA signaling and drought tolerance: integrating systems biology and whole plant physiology (Co-PI)

• NSF MCB-0618402, Arabidopsis 2010: Towards a comprehensive Arabidopsis protein interactome map: Systems biology of the membrane proteins and signalosome (Co-PI)

• NSF CCF 0643529, CAREER: Graph theoretical inference and predictive dynamic modeling of signal transduction networks (PI)

• Human Frontiers of Science Program RGP20/2007, Mechanisms regulating the dynamics of a parasite community in a wild herbivore system (Co-PI)

• NIH 1R56AI065507-01A2, Emergence of human pathogens in the genus Bordetella (Co-PI)

• NSF EF 0742373, Quasispecies Network Theories for the Cross-Scale Evolutionary Dynamics of Pathogens (Co-PI)

Research Areas

Signaling Network Model of Cytotoxic T lymphocytes in T-LGL Leukemia

Cytotoxic T lymphocytes (CTL) are a group of CD8+ T lymphocytes that are essential for eliminating infected somatic cells and tumor cells. T-cell large granular lymphocyte (T-LGL) leukemia features a clonal expansion of antigen-primed CTL that successfully escaped activation induced cell death (AICD), a process that normally occurs after CTL activation. This disease provides us a unique opportunity to decipher the key mediators of CTL activation and AICD in humans. Our collaborative study focuses on developing a model that describes the signaling network involved in maintaining long-term survival of competent CTL in humans. This model will be used to identify potential therapeutic targets for T-LGL leukemia as well as to generate long-term competent CTL necessary for tumor and cancer vaccine development.

Collaborators:

• Thomas P. Loughran, M.D., Director of the Penn State Cancer Institute

Signal transduction in plant guard cells

Plants have developed sophisticated signal transduction mechanisms to be able to respond to changing environmental conditions. One such mechanism is the closing of stomata (pores) in response to drought conditions to curb excessive water loss. We are synthesizing experimental information on drought signaling to reconstruct and model the signal transduction network of abscisic acid-induced stomatal closure.

Collaborators:

• Prof. Sarah Assmann, Waller Professor of Biology, Department of Biology, Penn State

Relevant publications:

• Song Li, Sarah Assmann and Réka Albert
  Predicting essential components of signal transduction networks: dynamic model of guard cell abscisic acid signaling
  PLoS Biology 4 (10): e312, 2006 | read synopsis

Innate immunity is the most ancient and conserved immune response, and it is responsible for the early detection of potentially pathogenic microorganisms. Upon recognition of microbes by innate immune cells, diverse signaling pathways are activated that combine to eliminate the threat and initiate adaptive immune responses. We are developing models of the innate immunity on both the systemic and signal transduction level.

Collaborators:

• Dr. Eric Harvill, Associate Professor of Microbiology and Infectious Disease, Department of Veterinary Science, Penn State

Relevant publications:

• J. Thakar, M. Pilione, G. Kirimanjeswara, E. Harvill and R. Albert
  Modeling Systems-Level Regulation of Host Immune Responses
  PLoS Computational Biology (2007)

• Jaewook Joo, Michelle Gunny, Marisa Cases, Peter Hudson, Réka Albert, Eric Harvill
  Bacteriophage-mediated competition in Bordetella bacteria
  Proceedings of the Royal Society B  273, 1843-1848 (2006)

Modeling Drosophila embryonic segmentation

The complex interaction network between the segment polarity genes maintains their stable expression during embryonic development. We are developing a qualitative boolean model of the functioning of this network. Our findings suggest a remarkable robustness of the segmentation process, but also mechanisms that can derail the wild type development.

Collaborators:

• Prof. Hans Othmer, Professor, School of Mathematics , University of Minnesota
• Prof. Eduardo Sontag, Professor , Department of Mathematics, Rutgers Universty
• Dr. Madalena Chaves, Research Scientist, INRIA, France

Relevant publications:

• Madalena Chaves and Réka Albert
  Studying the effect of cell division on expression patterns of the segment polarity genes
  Journal of the Royal Society Interface, 2008 (in press)

• Madalena Chaves, Eduardo D. Sontag and Réka Albert
  Methods of robustness analysis for Boolean models of gene control networks
  IEE Proceedings in Systems Biology 153, 154-167 (2006)

Gene and Protein Networks

Timecourses of gene expression can be used to infer regulatory networks. We are studying the topology of the resulting networks and identifying conserved interaction motifs such as feedforward or feedback loops.

Collaborators:

• Prof. Costas Maranas, Professor , Chemical Engineering, Penn State
• Dr. Kateryna Makova, Assistant Professor, Department of Biology, Penn State
• Dr. Istvan Albert, Research Associate , Bioinformatics Consulting Center, Penn State

Relevant publications:

• Wen-Yu Chung, Réka Albert, Istvan Albert, Anton Nekrutenko and Kateryna D. Makova
  Rapid and Asymmetric Divergence of Duplicate Genes in the Human Gene Coexpression Network
  BMC Bioinformatics 7 : 46  (2006)

• Claire Christensen, Anshuman Gupta, Costas D. Maranas, and Réka Albert
  Inference and graph-theoretical analysis of Bacillus Subtilis gene regulatory networks
  Physica A  373, 796-810 (2007)