1. Stochasticity of gene expression in fluctuating environments

Cells encounter physicochemical fluctuations in their environment on a routine basis. Bacterial cells have developed regulatory mechanisms to cope up with many of these stress fluctuations. The response of the cells to different stresses may depend on the type, magnitude and the duration of the stress. We are investigating how the cellular stochasticity changes under different environmental fluctuations in order to learn the intricacies of the underlying gene regulatory network.
2. Adaptation bottlenecks and evolution of bacteria. 

A vast majority of bacteria and archaea can grow in diverse environmental conditions. Those conditions include high
pressures, high temperature, low temperature, high salinity, low pH, and high pH. Because these conditions are not 
hospitable for other life forms, these organisms have been named extremophiles. Adaptation of these organisms 
to such harsh conditions raises many interesting questions, such as how do they adapt to these conditions? Does 
the adaptation occur at a single-component level such as by mutations in proteins leading to their barostability and 
thermostability, or does the adaptation to these conditions have a collective nature, in which more than one cellular 
component acts in compliance to preserve the functionality of the other? We are trying to bottleneck cellular 
processes which undergo higher evolutionary pressures as a part of the adaptation of extremophiles to extremes of 
physicochemical conditions. 

3. Extreme eukaryotes and their evolution

Phylogenetic studies of evolution of ribosomal RNA places extremophiles, organisms growing in extremes of physical and chemical conditions, very close the last common universal ancestors, and hence provide invaluable source of understanding early life and their evolution. While most of the studies on extremophiles have focused on prokaryotes, there are many eukaryotes that have now been known to thrive in extreme conditions. Understanding adaptation of extreme eukaryotes requires understanding cellular and gene expression changes in eukaryotes which grow at normal conditions. Our lab has started to investigate how a single cell eukaryote responds to changing physical conditions, using a well studied single cell eukaryote, S. cerervisae. 

4. Genomics and evolution of extremophiles

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To what extent is genomic amino acid composition broadly dictated by physical and chemical properties instead of natural selection or chance? Most studies focus on the effect of amino acid alterations on functional properties of proteins or gene families. Yet the landscape upon which an organism evolves is ultimately related to constraints on its amino acid repertoire. Likewise, the existence of universal patterns in amino acid usage across vast evolutionary distances could  indicate fundamental properties relevant to all life. The genome sequencing of many extremophiles has created an opportunity to probe these basic, yet practical questions. Extremophiles have been sequenced at both vast evolutionary distances and across a broad range of environmental conditions. Hence these organisms provide a deep-field lens for resolving how variations in physiochemical environment alter genome characteristics.

5. Effect of pressure and temperature on autocatalytic activity of small RNAs

RNA is hypothesized as a primordial molecule due to its ability to form efficient catalysts and its similarity to DNA, where it can act as a molecular information machinery. Many studies indicate that these small RNAs may act like primitive tRNA. Furthermore, due to rich chemistry of the reactive gases, and dissolved elements, a reminiscence of the early earth, hydrothermal vents are hypothesized to offer conditions viable for the origin of life. It naturally gives rise to questions on whether these small RNAs, candidates for primordial life, could function at high pressures and temperatures. Our lab is trying to answer these questions by using computational modeling of RNA combined with experiments to investigate the plausible pressure-temperature phase diagram of the functionality of self-catalytic RNAs.

6. Anomalies of liquid water and liquid-liquid phase transition in supercooled water

For a number of decades, the anomalous behavior of water, e.g., the increase of density upon heating and the increase of diffusivity upon compression, has been the subject of intense research. More than 80 anomalies of water have been discovered in experiments. Some of these anomalies concern static thermodynamic properties, e.g., the increase of compressibility and specific heat when the temperature is decreased, and others concern dynamic properties, e.g., the breakdown of the Stokes–Einstein relation and the non-Arrhenius to Arrhenius dynamic crossover at low temperatures.To explain the anomalous behavior of water, the existence of a liquid–liquid (LL) phase transition has been proposed, but this hypothesized LL transition lies in a region of the pressure–temperature phase diagram inaccessible to experimentation on bulk water due to crystallization of the liquid within experimental time scales. Fortunately, the crystallization within this temperature region occurs at microsecond time scales, but the density relaxation of liquid is in the range of tens of nanoseconds (Figure 1). Thus, because of this rapid relaxation time, it is possible to study the metastable equilibrium behavior of liquid water at low temperatures using computer simulation.

7.Transport properties of liquid in supercooled state