Drug resistance is a major crisis worldwide with emergence of human pathogens that are resistant to multiple drugs (e.g., multidrug resistant S. aureus, TB). Drug resistance has also been observed in cancer. One of our major goals is to understand the cellular processes that generate resistance in great detail from a systems-level perspective. Such an understanding can help us design better treatment strategies and can help minimize resistance evolution. A second interest of the lab is to understand the causes of phenotypic heterogeneity in isogenic populations. Genetically identical cells in a microbial population in identical environment often exhibit a wide variety of phenotypes. An example of such heterogeneity is the presence of a small number of persister cells in a microbial population. Our goal is to elucidate the molecular mechanisms underlying such phenotypic heterogeneity. A third goal of the lab is to connect phenotypic heterogeneity with long-term evolution of cellular phenotypes – e.g., how phenotypic variations present in a microbial population can influence long-term evolution of drug resistance. In addition, we are generally excited about understanding the inner workings of complex biological systems and evolution of such systems.
Our work is highly interdisciplinary in nature. In addition to basic microbiology and molecular biology techniques, we use FACS, fluorescence microscopy, Next Generation Sequencing, computational techniques and mathematical modelling to address our research questions.
Open positions: I am looking for talented and motivated Postdocs and PhD students in both experimental and computational domains. Applicants with a background in Biological Sciences, Bioinformatics, Physics, Mathematics, Computer Science, or Mechanical Engineering with an interest in understanding of complex biological systems are welcome to apply. If you are interested in joining the lab, please email me your CV along with a brief statement of your research interest.
Changes in gene expression predictably shift and switch genetic interactions. by Li X., Lalic J. , Baeza-centurion P. , Dhar R. , Lehner B. Nature Communications 10 3886- (2019)
Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation by Dhar R., Missarova A. M., Lehner B. , Carey L. B. eLife 8 - (2019)
A Concentration-Dependent Liquid Phase Separation Can Cause Toxicity upon Increased Protein Expression by Bolognesi B., Gotor N. L., Dhar R. , Cirillo D. , Baldrighi M. , Tartaglia G. G., Lehner B. Cell Reports 16 222-231 (2016)
Slow growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage. by David van Dijk, Riddhiman Dhar, Alsu Missarova, Lorena Espinar, Will Blevins, Ben Lehner, and Lucas Carey. Nature Communications 6 - (2015)
Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes. by Riddhiman Dhar, Tobias Bergmiller, and Andreas Wagner. Evolution 68 1775-1791 (2014)
Yeast adapts to a changing stressful environment by evolving cross-protection and anticipatory gene regulation. by Riddhiman Dhar, Rudolf Sägesser, Christian Weikert and Andreas Wagner. Molecular Biology and Evolution 30 573-588 (2013)
Adaptation of Saccharomyces cerevisiae to saline stress through laboratory evolution. by Riddhiman Dhar, Rudolf Sägesser, Christian Weikert, Ju Yuan and Andreas Wagner. Journal of Evolutionary Biology 24 1135-1153 (2011)
Interface of apoptotic protein complexes has distinct properties by Mitra P., Dhar R. , Pal D. In Silico Biology 9 365-378 (2010)
Analyzing the catalytic mechanism of protein tyrosine phosphatase PtpB from Staphylococcus aureus through site-directed mutagenesis. by Somnath Mukherjee*, Riddhiman Dhar*, and Amit Kumar Das. International Journal of Biological Macromolecules 45 463-469 (2009)
Protein-Protein Interaction in Apoptosis Process by Dhar R., Mitra P. , Pal D. International Conference on Bioinformatics (InCoB 2006) 287- (2006)
Emergence of Resistance to New Antibiotics through Mutations and Higher Order Epistatic Interactions Science and Engineering Research Board (SERB)
Causes and Consequences of Phenotypic Plasticity in Microbial Populations ISIRD, SRIC
Microbial Cell Factories for Isobutanol Production using Metabolic Engineering Apex Committee of SPARC
Area of Research: Systems Biology
Area of Research: Systems Biology
Area of Research: MEMS based micro-fluidic systems for drug delivery
Area of Research: Epistatic interactions
Area of Research: Gene and Process Scale Engineering
Area of Research: Computational Systems Biology