Sriram Lab:Research

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Fig. 1. Putative metabolic pathways in the marine diatom Phaeodactylum tricornutum investigated by us through isotope-assisted metabolic pathway analysis. Click for higher resolution and detail; see Fig. 2 for isotope-assisted analysis of some of these pathways. From this publication.

The Sriram Lab's research is focused on two related areas: metabolic engineering and systems biology. Metabolic engineering is the rational modification of organisms to improve their cellular properties or performance. Systems biology is the holistic, quantitative analysis of large-scale biological datasets toward improved understanding, prediction and control of how a cell, tissue or organism behaves. Both these are very rapidly growing, interdisciplinary research areas with immense potential for chemical engineers to uniquely apply their expertise.

Fig. 2. Isotope-assisted metabolic pathway analysis in the marine diatom Phaeodactylum tricornutum reveals evidence for flux through the Entner-Doudoroff (ED) pathway. Click for higher resolution and detail; see Fig. 1 for pathways. From this publication.

In particular, we analyze and engineer metabolic and gene regulatory networks in living systems. Metabolic pathways are "traffic maps" of carbon and other elements within cells (Fig. 1) and gene regulatory networks (Fig. 3) show how protein-DNA interactions control cellular activities. Such analyses provide several nontrivial insights, including strategies to relieve metabolic bottlenecks and boost cellular performance by manipulating select genes.

thumb|Fig. 3. An Arabidopsis transcription factor-gene regulatory network as quantitatively deduced by network component analysis. SVG file; click twice (once here and once on the subsequent page) for full figure in high resolution. From [http://www.biomedcentral.com/1752-0509/7/126/abstract this publication].

Toward these objectives, we combine experimental techniques such as isotope labeling, two-dimensional (2-D) NMR, gas chromatography-mass spectrometry (GC-MS), DNA microarray analysis and quantitative RT-PCR (qPCR) with several computational techniques for metabolic flux/pathway analysis and gene regulatory network deduction (Figs. 2, 3).

Many of our applications focus on plants and related systems. The plant kingdom is the primary source of several commodities crucial to an economy such as food, biofuels, fiber, several high-value therapeutics and recently, renewable chemical industry feedstocks. Highly sophisticated plant metabolic networks synthesize these commodities from thin air (CO₂), light and minerals. Quantitative studies of plant networks open up the prospect of smartly engineering these networks for beneficial purposes, and therefore hold much promise for a sustainable future. We also study bacterial, yeast and mammalian cells. Investigations of networks in these cells enable their metabolic engineering for the production of select high-value chemicals, or provide insights on how biological networks are perturbed due to the lack of function of a gene or genes in genetically inherited diseases.