Systems Biology

Modeling chronic kidney disease (CVD) for diagnostic and personalized management

CVD is a complex disease involving signaling, immune and metabolic perturbations along with perturbed flux across kidney. This causes nutrient imbalance leading to whole body perturbations. The project deals with developing a system perspective model to represent pathophysiology of CVD.

Synthetic biology and metabolic engineering of cyanobacteria

Cyanobacteria or blue-green algae are a group of prokaryotes well known for their ability to carry out oxygenic photosynthesis. These photoautotrophs show greater photosynthetic efficiency, simpler genetic structures and faster growth compared to terrestrial plants and green algae.  Moreover, cyanobacteria can be engineered genetically and can grow on non-arable land, waste-water and seawater.  These properties make cyanobacteria an interesting host for biotechnological applications.

Open problems in evolutionary biology (experiments and/or theory)

Evolution of life over the last >3.5 billion years has shaped the life forms that we presently see on the planet. Developments in genome sequencing and molecular biology allow us to perform evolutionary experiments in lab, and see in real time, how environment shapes changes in a population. Understanding this relationship between the environment and the changes that take place in the DNA of an organism is the focus of our lab's research. We perform theory and also perform experiments (using yeast and bacteria) to answer questions of interest.

Orchestration of cancer cell response

Tumor necrosis factor-alpha (TNFa), an inflammatory cytokine present in large quantities in a tumor microenvironment, is strongly implicated in various cancer cell responses.  The objective of this project is to understand the orchestration of response of cancer cells exposed to a drug cocktail. The project will involve static and discrete dynamical modelling of activated TNFa signalling network consisting of biochemical reactions, curated in-house.

Phenotype switching during TNFa signaling

Tumor necrosis factor alpha (TNFa), a pleiotropic cytokine capable of exhibiting pro-survival, apoptosis, or necrotic phenotypes, is implicated in several cancers. Signal flow leading to these multitude of context-specific responses is orchestrated by underlying molecular network consisting of nodes such as proteins, genes connected by interactions between them. This leads to a question as to what are the topological properties of the network that dictate the context-specific responses and how to modulate these to favour a desired phenotype.

Apoptosis modulation in cancer cells

Tumor necrosis factor alpha (TNFa), a pleiotropic cytokine capable of exhibiting pro-survival, apoptosis, or necrotic phenotypes, is implicated in several cancers. Understanding the underlying mechanism that governs a cell’s decision to apoptotic phenotypic response, a desired outcome, can help obtain insights on how signal flow to cell-death can be modulated. This leads to a question as to what intracellular interventional strategies could be employed to manipulate signal flow to cell-death state.

Biochemical signaling network for periodic forcing within sperm flagella.

Sperm motility is critical to fertilization and reproduction in animals. There remain several gaps in the knowledge base about the signaling mechanisms that govern conversion of chemical energy to mechanical work leading to flagellar beating as well sperm steering and homing. The goal of this study is to build biochemical networks from available literature and propose models that explain and predict sperm motility in response to chemo-attractive molecules. We intend to use of MATLAB® for this project.

Modeling autoimmune disorders

Immune cells help fight infections, but if fights host cells, the pathological condition is that of autoimmune disorder. When does such a phenotype occur. What are the conditions that leads to such a state? Modeling of immune system complexity will be carried out to explain some of these questions for specific diseases.