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 for improvement of their cellular properties. Systems biology is the holistic, quantitative analysis of large-scale biological data sets toward improved understanding, prediction, and control of how a cell 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.
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[[Image:Labeling expt Sriram.jpg|thumb|right|375px|'''Quantifying carbon traffic by isotope-assisted metabolic flux analysis.''' Click for detail.]]
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[[Image:Labeling expt Sriram.jpg|thumb|center|400px|'''Quantifying carbon traffic by isotope-assisted metabolic flux analysis.''' Click for detail.]]
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The Sriram Lab's research is focused on two related areas: <b>metabolic engineering</b> and <b>systems biology</b>. 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.
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We analyze and engineer metabolic and gene regulatory pathways of plants and mammalian cells. Metabolic pathways are "traffic maps" of carbon and other materials within cells, and gene regulatory pathways are networks showing how this traffic is controlled by the cell. Such analysis provides insights into bottlenecks existing in the cell, and how these can be improved by engineering the pathways. 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 deduction of gene regulatory networks.
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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.  
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[[Image:Soybean 2D HSQC.jpg|thumb|center|250px|'''Two-dimensional [<sup>13</sup>C, <sup>1</sup>H] NMR spectrum of protein hydrolysate from soybean embryos.''' Click for detail.]]
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[[Image:Soybean 2D HSQC.jpg|thumb|left|300px|'''Two-dimensional [<sup>13</sup>C, <sup>1</sup>H] NMR spectrum of protein hydrolysate from soybean embryos.''' Click for detail.]]
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[[Image:H4IIE flux map (GK2 2 colors).jpg|thumb|center|250px|'''Global metabolic changes due to glycerol kinase overexpression in rat liver cells.''' Click for detail.]]
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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.
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[[Image:H4IIE flux map (GK2 2 colors).jpg|thumb|right|175px|'''Global metabolic changes due to glycerol kinase overexpression in rat liver cells.''' Click for detail.]]
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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 (CO<sub>2</sub>), 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.
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We also study mammalian and yeast cells. Mammalian cell cultures provide a means to understand genetically inherited diseases in greater detail, particularly 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.
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Studying plants in this way is expected to have significant impact on today's economy because plants are the primary sources of food, biofuels and several specialty chemicals such as pharmaceuticals. Mammalian tissue 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.
 
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Revision as of 08:54, 11 August 2009

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

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.

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.

Two-dimensional [13C, 1H] NMR spectrum of protein hydrolysate from soybean embryos. Click for detail.
Two-dimensional [13C, 1H] NMR spectrum of protein hydrolysate from soybean embryos. Click for detail.

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.

Global metabolic changes due to glycerol kinase overexpression in rat liver cells. Click for detail.
Global metabolic changes due to glycerol kinase overexpression in rat liver cells. Click for detail.

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 mammalian and yeast cells. Mammalian cell cultures provide a means to understand genetically inherited diseases in greater detail, particularly 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.

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