There are a large number of research topics being addressed by faculty in the Department of Biological Chemistry. However, the portfolio of research projects falls into four broad areas that include regulation of gene expression, signal transduction, protein folding and processing, and structural enzymology. Investigators in the department bring to bear a broad range of technologies to address important biomedical questions from a biochemical perspective. This emphasis on the molecular mechanisms of life is further strengthened by our close ties and cross-appointments with the Chemistry Department and Biophysics Research Division on the main campus, making the Department of Biological Chemistry the centerpiece of a large and diverse biochemical community at the University of Michigan.
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The research of faculty in the Biochemical Signaling area probes the molecular mechanisms accounting for changes in cell metabolism that mediate the physiological adaptation of living cells in response to alterations in their environment. Often these cellular responses involve sequential biochemical reactions that form signaling cascades to coordinately regulate multiple cell functions. Some of the biochemical mechanisms studied in these signaling cascades include posttranslational modifications of proteins such as phosphorylation, methylation and ubiquitination. Other mechanisms involve allosteric regulation of molecular function, including protein-protein and protein-DNA interactions. The goal of all of these studies is to understand the principles of coordinated molecular regulation at a biochemical level and to demonstrate the importance of these biochemical regulatory mechanisms in a cellular context.
Enzymes play central roles in all metabolic and cellular signaling pathways. Many investigators in the department are interested in understanding how enzymes function at the molecular and atomic level through a combination of modern biochemistry and structural biology. Techniques which are being employed to investigate enzyme structure and dynamics include X-ray crystallography, NMR, mass spectroscopy and protein chemistry, while their chemical behavior is being characterized by rapid-reaction and steady-state kinetics, calorimetry, chemical analyses, and a variety of spectroscopies. Protein engineering is being used to study how structure determines function. Through the use of these techniques, investigators are able to probe mechanism and specificity in order to gain a greater understanding of how enzymes work and how they function in the context of molecular pathways in the cell. Such knowledge could provide the basis for new medical treatments, pollution-control strategies, or many other applications.
All newly-synthesized polypeptides have to be folded into their three-dimensional structures to be functional. Many proteins have to reach destinations other than cytosol, the site where protein synthesis occurs. In addition, a majority of proteins constantly undergo post-translational modification in response to a wide variety of cellular signals. Therefore, understanding mechanism and regulation of protein folding, protein translocation and protein processing is an integral part of modern molecular and cell biology. In addition, errors in these processes cause diseases ranging from Alzheimer's to Diabetes. Protein folding and processing is one of the major research focuses in our department. Faculty in this area engage in a number of research topics including the unfolded protein response; structure and function of molecular chaperones; heat shock response; protein misfolding in aging and disease; bacterial type III secretion; yeast pheromone processing; protein transport in the secretory pathway; protein targetting and organelle biogenesis.
The control of gene expression is regulated in a highly organized fashion to ensure specific genes are expressed at the appropriate times and levels in response to various genetic and environmental stimuli. In eukaryotes, gene expression is controlled at multiple levels from transcription factor-mediated recruitment of the basal transcription machinery at specific gene promoters to processing and maturation of the RNA transcript. Disruption of these events in humans contributes to many pathologies including cancer, metabolic syndromes, and developmental disorders. Faculty who are investigating the regulation of gene expression are interested in numerous topics including transcriptional regulatory pathways in pro- and eukaryotes, DNA and RNA interactions with proteins, RNA processing and the functions of catalytic RNA, chromatin modification and remodeling, and three-dimensional organization of genes in the nucleus. Research employs a variety of model organisms and utilizes an array of modern techniques in biochemistry and molecular, cellular, and structural biology to elucidate the mechanisms that govern gene expression in pro- and eukaryotes.