Systems Biology and Biological Regulation Research

Systems Biology and Biological Regulation research seeks to characterize the structural, biochemical, and in vivo functional properties of individual biomolecules and pathways with the cutting-edge approaches of modern genomics, proteomics, and metabolomics. It combines both experimental and computational approaches to model biological systems and tests the predictions of the models.

Investigators in this focus area are addressing questions concerning such topics as gene regulation at both transcriptional and post-transcriptional levels, metabolic regulation and homeostasis, regulation of cell shape and motility, intracellular transport and compartmentation, phylogenomics, and molecular evolution.

Faculty Research Summaries

Sriram Kosuri

Professor Sri Kosuri and his lab develop technologies to make the elucidation and engineering of biological systems faster and simpler. They apply these technologies to uncovering mechanisms in gene regulation, as well as emerging applications in synthetic biology. In particular, the laboratory develops and combines three recent technologies: DNA synthesis, DNA sequencing, and genome engineering. First, they develop methods to build large libraries of synthetic DNA sequences using low-cost DNA microarrays. This allows them to build thousands to millions of designed constructs for modest cost. Second, they develop new measurement technologies using next-generation sequencing that allows them to test the functionality of these synthetic DNA libraries simultaneously. Finally, using new genomic engineering technologies, they can do these large-scale synthesis/sequencing experiments in a wide-variety of cell types and organisms.

James U. Bowie

Professor James Bowie and his group are fascinated by protein structure, folding and stabilization. This interest has led them into three main areas: (1) learning how membrane proteins fold and how they can be stabilized; (2) the structures and biological functions of a biological polymer they discovered, that is formed by a very common protein module called a SAM domain; (3) developing and stabilizing enzyme pathways for the production of biofuels.

Guillaume F. Chanfreau

Professor Guillaume Chanfreau's laboratory is interested in gene expression regulation in eukaryotic cells, with a particular emphasis on post-transcriptional steps. Within this large field, they are focusing on understanding how cells degrade RNAs that arise from malfunctions in gene expression pathways ("RNA surveillance"). In particular, they are analyzing the functions of the double-stranded RNA endonuclease RNase III and of the nonsense-mediated decay pathway in RNA surveillance, and how these enzymes regulate gene expression.

Catherine F. Clarke

Professor Catherine Clarke and the Clarke lab study the biosynthesis and functional roles of coenzyme Q (ubiquinone or Q). Q functions in mitochondrial respiratory electron transport and as a lipid soluble antioxidant. The group is using the yeast Saccharomyces cerevisiae (bakers yeast) to elucidate the biosynthetic metabolism of Q. Their experimental approach employs a combination of molecular genetics, lipid chemistry and biochemistry to delineate the steps responsible for Q biosynthesis.

Steven G. Clarke

A major interest of Professor Steven Clarke's Laboratory is understanding the biochemistry of the aging process. The group is particularly interested in the generation of age-damaged proteins by spontaneous chemical reactions and the physiological role of cellular enzymes that can reverse at least some portion of the damage. They have focused their efforts on the degradation of aspartic acid and asparagine residues and the subsequent metabolism of their racemized and isomerized derivatives. The group is presently determining the biological role of protein methyltransferases that can initiate the conversion of D-aspartyl residues to the L-configuration as well as the conversion of isopeptide linkages to normal peptide bonds. Such "repair" reactions may greatly increase the useful lifetime of cellular proteins and may help insure organismal survival. View Professor Clarke's YouTube Lecture

Robert T. Clubb

Professor Robert Clubb investigates the molecular basis of bacterial pathogenesis. In particular, they study how microbes display and assemble cell wall attached surface proteins, and how they acquire essential nutrients from their host during infections. The group's study could lead to creating new inhibitors of bacterial infections.

Albert J. Courey

Professor Albert Courey and his group study the molecular basis of cell development. During embryogenesis, a cluster of apparently undifferentiated cells is transformed into an ordered array of differentiated tissues. Using Drosophila as a model system, his research group combines biochemical and genetic approaches to study the molecular basis of this amazing transformation. Essentially all the regulatory circuits they study are conserved throughout the animal kingdom. Therefore, their studies have important implications for human health and development.

Juli Feigon

Professor Juli Feigon and her research group study nucleic acid structure and specific recognition of nucleic acids by proteins. Her group focuses on determining the three-dimensional structures of DNA and RNA, and on investigating their interactions with various proteins and ligands, and to study nucleic acid folding.

Carla M. Koehler

Professor Carla Koehler and her research group encompass two major areas: Understanding the mechanism of protein import into mitochondria and determining the process by which defects in mitochondrial protein translocation lead to disease.

James C. Liao

Professor James Liao and his group focus on metabolism, including its biochemistry, extension, and regulation. His group uses metabolic engineering,synthetic biology, and systems biology to construct microorganisms to produce next generation biofuels and to study the obesity problem in human. Their ultimate goal is to use biochemical methods to replace petroleum processing and to treat metabolic diseases.

Joseph A. Loo

The research interests of Professor Loo's group include the development and application of bioanalytical methods for the structural characterization of proteins and post-translational modifications, proteomics-based research, and the elucidation of of disease. The composition and structure of noncovalently-bound protein-protein and protein-ligand interactions are studied by electrospray ionization mass spectrometry and ion mobility.

Sabeeha S. Merchant

The Merchant research program focuses on trace metal metabolism using Chlamydomonas as a reference organism. The group uses a combination of classical genetics, genomics and biochemistry to discover mechanisms of trace metal homeostasis in Chlamydomonas, especially mechanisms for reducing the quota or for recycling in situations of deficiency.

Margot E. Quinlan

Professor Margot Quinlan and her group use biochemistry, microscopy and genetic approaches to study regulation of the actin cytoskeleton. The group is currently focused on Spire (Spir) and Cappuccino (Capu), two proteins that collaborate to build an actin network essential for early body axis development. Combining an in vitro understanding of the mechanism of Spir and Capu with in vivo studies of polar cells will provide insight into how the actin cytoskeleton is regulated and a broader understanding of cell polarity.

Emil Reisler

Professor Emil Reisler's group investigate cell motility and force generation mechanism of actin, tubulin, and a family of motor proteins. The aim of these studies is to obtain a structural description of the mechanism of motion and force generation. At the cellular level, the group studies the function, interactions, and structural transitions of the assembled protein systems.

Yi Tang

Professor Yi Tang's research lab is interested in natural product biosynthesis and biocatalysis. In the natural product area, they are interested in elucidating biosynthetic pathways of polyketides, nonribosomal peptides and related compounds. Their goal is to understand the biochemical and structural basis of different enzymes encoded in these pathways. In particular, they are studying the biosynthesis of aromatic polyketides from Streptomyces and iteratively biosynthesized compounds from filamentous fungi. By accumulating biosynthetic knowledge and enzymatic tools, they aim towards the engineered biosynthesis of unnatural natural products through combinatorial biosynthesis.

Jorge Torres

Professor Jorge Torres’ research group is interested in understanding the mechanisms of cell division. Currently they are discovering and characterizing novel enzymatic activities that are critical for cell division (cancer targets) and discovering or designing small molecules that can inhibit their function (anti-cancer agents). To do this, they are taking multidisciplinary approaches that utilize human cancer cell lines and high throughput proteomic and small molecule screening with a combination of disciplines, including biochemistry, cell biology, chemoinformatics, chemical biology and microscopy.

Roy Wollman

The Wollman lab is interested in understanding principles of information processing in intracellular and intercellular signaling networks in the presence of a high degree of single-cell variability. The lab utilizes a systems biology approach that merges computational and experimental tools with a focus on microscopy and single cell dynamics.