Amyotrophic Lateral Sclerosis

The broad area of our research in the investigation of mechanisms of neurodegeneration leading to diseases such as Alzheimer’s disease and Amyotrophic Lateral Sclerosis (ALS). We use computational and experimental methods to carry out our work. The computational methods of interest to us include Network Theory, Nonlinear Systems Analysis and Feedback Control. We use these methods to analyse experimental data, to create new algorithms to address large-scale gene regulatory networks and develop hypothesis that can be tested by directed experiments. The recent focus of our research has been Amyotrophic Lateral Sclerosis in Indian patients. We analysed the genetic basis of ALS in Indian population and determined the frequency of the hexanucleotide repeat expansion in C9orf72 and the trinucleotide (CAG) repeat expansion in ATXN2 in Indian ALS patients. Using targeted NGS analysis, we identified variants associated with ALS (known variants), rare variants (present at extremely low frequency in ExAC database) and novel variants (absent in our healthy controls and ExAC). We are working on the mutations discovered in Indian ALS patients, for example, mutations in D-amino acid oxidase (DAO) gene. This D-amino acid degrading enzyme plays an important role in motor neuron degeneration through D-serine regulation. The mutation which has been predicted as damaging by Poly Phen-2, SIFT, Mutation taster, is being studied to elucidate destabilizing and activity altering mechanisms through molecular dynamic simulations, biochemical and cell culture methods to understand neurodegeneration. Some of the other genes are OPTN, SQSTM1, MATRIN3 and TDP43. We are now consolidating the results and creating a gene regulatory network to carry our computational analysis to understand the onset and progression of hte disease.

Advanced Bioprocess Control

Bioprocesses are intrinsically nonlinear and required special attention when strategies are developed to control bioreactors. We have developed and implemented a range of advanced and novel controllers such as the Decoupled Input-Output Linearizing Controller (DIOLC), Decoupled Adaptive Controller, Sequential Adaptive Network (SAN) Controllers, Self-Organizing Network Controllers and the Permissible Metabolic Regime Controllers. These are being used by the team in Biopharmaceutical CoE.