Biochemical and Biological Engineering
Metabolic Engineering
Systems Biology
The Metabolic Inquiry and Cellular Engineering (MICE) Lab, uses systems approaches (both experimental and computational) to understand biological cell behavior and function. We build computer models of the cell through genome-scale metabolic network reconstruction and compute cell phenotype using constraints-based flux balance analysis. We are also involved in building metabolic reconstructions using QC/QA protocols and algorithms for incorporating experimental data as constraints. Experimental approaches in prokaryotes involve genome-engineering of Escherichia coli for value added chemicals using recombinant and synthetic biology techniques. The spectrum of products we are interested in range from drug molecules like violacein, non ribosomal peptides like penicillin and biopolymers like polyhydroxyalkanoates.
We also investigate drug resistance in cancer cells and pathogens using systems approaches. Our model systems to probe antibiotic resistance are chromobacterium violaceum, a zoonotic pathogen. We have used systems approaches to identify benign metabolite supplementation strategies to resensitise populations resistant to antibiotics. Currently we are also involved in exploring host-pathogen interactions and antibiotic resistance through integrated metabolic network reconstructions and models for the ESKAPE pathogen Klebsiella pneumoniae.
Our efforts to delineate an integrated paradigm for chemotherapeutic resistance in glioblastoma also involve many systems biology approaches including exome sequencing, metabolomics, transcriptomics and respiromics. We investigate metabolic reprogramming in temozolomide susceptible and resistant cells using scalable approaches using constraints-based flux balance models.We strive to practice model-driven science by validation of in silico discoveries experimentally at different levels of molecular organization in both prokaryotic and eukaryotic systems.
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