Sriram Lab:Research

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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 interdisciplinary fields with immense potential for chemical engineers to uniquely apply their expertise as well as very rapidly growing research areas.

Quantifying carbon traffic by isotope-assisted metabolic flux analysis. Click for detail.

We analyze and engineer metabolic and gene regulatory pathways in living systems. Metabolic pathways are "traffic maps" of carbon and other elements within cells (see figure below right) and gene regulatory pathways are networks showing how this traffic is controlled by the cell. Such analysis provides insights into how metabolic bottlenecks can be relieved and how cellular performance can be boosted by engineering select genes.

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.

Our applications focus on plants and related systems as well as mammalian and yeast cells. Plants are the primary sources of several commodities crucial to an economy such as food, biofuels, fiber, several high-value therapeutics and recently, 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. Studies of mammalian cell networks are beneficial because mammalian cultures provide a means to understand human genetic diseases in greater detail, especially how biological networks are perturbed due to the lack of a gene or genes. Investigations of yeast networks enable the metabolic engineering of yeast for the production of select high-value chemicals.

Two-dimensional [13C, 1H] NMR spectrum of protein hydrolysate from soybean embryos. Click for detail.
Global metabolic changes due to glycerol kinase overexpression in rat liver cells. Click for detail.