Drug resistance is a major threat to our healthcare system and is a worldwide problem. Widespread use of antibiotics and drugs has resulted in cells acquiring resistance and they are often resistant to multiple drugs (e.g., multidrug resistant S. aureus, TB). Drug resistance is also observed in cancer where some cancer cells can survive anticancer treatments. Our aim is to understand the processes that generate resistance in great detail because this would help us design better treatment strategies. A second interest of the lab is to understand causes of phenotypic plasticity in isogenic populations. Genetically identical individuals in identical environment were thought to have identical phenotype (e.g., drug resistance). However, that is not the case. It has been known for quite some time now that a small number of cells in a microbial population can tolerate and survive very high drug concentrations. These cells are known as persisters. With the advent of single cell techniques, it is becoming even more clear that isogenic cells can and do show significant phenotypic differences. However, the causes of such differences in phenotype or the cellular processes that generate these differences are not well understood. A third aim of the lab is to connect phenotypic plasticity with long term evolution – how short term phenotypic variations (e.g., persistence) can influence long-term evolution of drug resistance. We use bacteria and yeast as model systems for our work. In addition to basic microbiology and molecular biology techniques, we use FACS, microscopy, high throughput sequencing and mathematical modeling to understand these processes better.
Open positions: I am looking for good, motivated Postdocs and PhD students in both experimental work and computational biology. If you are interested in joining the lab, please email me with your CV and a brief statement of research interest.
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)
Causes and Consequences of Phenotypic Plasticity in Microbial Populations ISIRD, SRIC
Area of Research: Systems Biology
Area of Research: Systems Biology
Area of Research: MEMS based micro-fluidic systems for drug delivery