个人简介

2008–present Assistant Professor, Chemistry, Carnegie Mellon University (Courtesy appointments in Physics and Biomedical Engineering) 2004–2008 Postdoctoral Research Fellow, University of California, Berkeley with Prof. Carlos Bustamante and Prof. Ignacio Tinoco Jr. 2002–2004 Postdoctoral Associate, Yale University with Prof. Ronald R. Breaker 2001 Ph.D. in Biophysics and Biochemistry, Center for Cellular and Molecular Biology, India Awards and Distinctions 2012 NSF-CAREER Award

研究领域

Bioorganic & Chemical Biology/Biophysical/Sensors/Probes & Imaging/Spectroscopy & Single Molecule Analysis

Prof. Mandal’s research focuses on understanding the conformational dynamics of RNAs and how these structures effect the progression of molecular motors such as RNA polymerase using structural, biochemical and single-molecule techniques. In the past decade, new methods have been developed to manipulate single-molecules that provide a novel way to directly measure the forces generated in biochemical reactions, and even alter the fate of these reactions by applying external forces. Moreover, these methods have been uniquely applied to track the structural conformations of single-molecules in real time. We use optical tweezers to exert forces on single-molecules, and then to record the molecular end-to-end extensions (force-extension curves). These experiments may shed new light on the RNA folding problem, and molecular motors that harness the RNA structural conformations to regulate gene expressions. Developing high resolution optical tweezers and other methods for nanotechnology and cell biology One of the major goals in my lab is to develop a high resolution optical tweezers that can measure the translocation of molecular motors at a single-base pair resolution with high precision. Several groups have developed this technology. At CMU, we are currently developing methods to use fluorescence detection along with the force and distance measurement. The tweezers will be used to study various biological processes related to diseased and normal cells. Mechanical folding of RNA molecules using optical tweezers RNA folding, which includes thermodynamic and dynamic folding, is one of the important problems in biophysics. Emergence of new classes of RNAs with regulatory functions such as riboswitches, non-coding RNAs, small RNAs has further highlighted this unsolved problem. One of the challenging issues is: How do these RNA molecules fold into unique structure? What is the role of small molecules and ligands? To understand the RNA folding problem, we are using riboswitches and other structural RNAs as model systems. Several experimental methods such as X-ray crystallography, NMR spectroscopy, fluorescence etc., have been applied resulting in high quality time-averaged snap shots of the structural information. We are addressing these folding problems by exerting mechanical forces using force ramp (force is changed continuously), constant force (force held at a constant set point) and force-jump (force is changed instantaneously to a higher or lower values) methods. Using optical-tweezers, these methods provide invaluable information on the disruption of molecular interactions and to measure their rate kinetics over a large range of forces. RNA polymerase and their role in gene regulation Transcription by RNA polymerase (RNAP) is one of the most exquisitely controlled processes in the cell. Several regulatory mechanisms control the rate of elongation in response to environmental responses. As transcription proceeds, the nascent transcript may fold into specific secondary structures that signal the transcribing polymerase to pause or to terminate transcription prematurely. Currently, studies are in progress to reveal the effect of accessory factors on the rate of elongation and how the nascent RNA folding alters progression of the transcriptional machinery.

近期论文

查看导师最新文章 （温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Mandal, M., Lee, M., Barrick, J.E., Weinberg, Z., Emilsson, G.M., Ruzzo, W.L., Breaker, R.R. A glycine dependent riboswitch that uses cooperative binding to control gene expression. Science. (2004), 306, 5694:275-279. Mandal, M., Breaker, R.R. Gene regulation by riboswitches. Nature Reviews Molecular and Cell Biology. (2004), 5 (6):451-463. Mandal, M., Breaker, R.R. Adenine riboswitches and gene activation by disruption of a transcription terminator. Nature Structural & Molecular Biology. (2004), 11(1): 29-35. Barrick, J.E., Korbino, K.A., Winkler, W.C., Nahvi, A., Mandal, M., Collins, J., Lee, M., Roth, A., Sudarsan, N., Jona, I., Wickiser, J.K., Breaker, R.R. New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control. Proceedings of National Academy of Sciences, USA. (2004), 101, 17, 6421-6. Mandal, M., Boese, B., Barrick, J.E., Winkler, W.C., Breaker, R.R. Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria. Cell. (2003), 113 (5): 577-86. Mandal, M., Nagaraj, R. Antibacterial activities and conformations of synthetic alpha- defensin HNP-1 and analogs with one, two and three disulfide bridges. Journal of Peptide Research. (2002), 59 (3): 95- 104. Mandal, M., Jagannadham, M.V., Nagaraj, R. Antibacterial activities and conformations of bovine beta- defensin and BNBD-12 and analogs: structural and disulfide requirements for activity. Peptides. (2002), 23, 3, 413-418.