Carnegie Mellon University Department of Chemistry

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The Department of Chemistry Welcomes New Faculty Member Maumita Mandal

photo of Maumita MandalDr. Maumita Mandal, whose research is at the interface of chemistry and biology, will join the Department of Chemistry as an assistant professor at the beginning of the 2008–2009 academic year.

Dr. Mandal’s research focuses on understanding the structural rearrangements in RNA molecules that function as “molecular switches.” These so-called riboswitches bind small molecules and change the way a gene is expressed into protein products, thus regulating gene expression in living organisms. Riboswitches undergo conformational changes upon binding small molecules called metabolites, which dictates whether the adjacent gene/ set of genes be switched “on” or “off.” However, in physiological conditions, it is often difficult to single out one existing conformation from others using biochemical methods, as the RNA molecules exist in partially folded and unfolded ensemble of conformations that masks the signal. Dr. Mandal plans to use force-sensitive optical-tweezers to accomplish this task. Optical-tweezers enable researchers to mechanically manipulate single-molecules by applying small forces in the order of piconewton (pN) accuracy. Specifically, Dr. Mandal plans to use these single-molecule manipulations to define the conformational dynamics and uncover how RNA molecules interact with ligands, proteins or other RNAs that are fundamental to RNA-based macromolecular complexes; to investigate the kinetics and thermodynamics underlying these interactions, and to determine how these structural rearrangements can be controlled to make genetic decisions.

Dr. Mandal’s interdisciplinary approach, which integrates molecular biology, biochemistry and chemical physics, will help her to understand the various facets of RNA metabolism and small-molecule dependent gene regulation that plays a crucial role in maintaining cellular homeostasis. “The totality of this approach should allow me to resolve basic questions on the allosteric regulation of gene expression that has fascinated scientists for decades and will open up new avenues of pharmaceutical research for exploration of structural RNAs as worthwhile drug targets,” said Dr. Mandal.

Dr. Mandal received her doctorate in Biophysics and Biochemistry from the Center for Cellular and Molecular Biology in Hyderabad, India. After earning her doctorate, Dr. Mandal was a postdoctoral researcher at Yale University. There she investigated novel mechanisms of RNA-mediated gene regulation involving riboswitches that act as metabolite sensors in cells. As a postdoctoral research associate at the University of California, Berkeley, she used single-molecule approaches to follow the conformational dynamics in real-time in guanine-riboswitch molecules. She discovered that the transcriptional machinery of the cell could make genetic decisions by utilizing the cooperative binding and energetic coupling of Mg2+ ions and ligand-dependent structural conformations in guanine-riboswitch.

June 11, 2007