Assistant Professor Ganesh Sriram
Ph.D., Iowa State University, 2004
Room 1208D Chemical and Nuclear Engineering Building
E-mail: gsriram@umd.edu
Phone: (301) 405-1261
Research Interests
Systems biology and metabolic engineering, metabolism and regulation in higher eukaryotes, fuel production from biorenewable resources, and genetically inherited metabolic disorders.
Research Statement
Prior Research
Doctoral
For my Ph.D., I worked on applying stable isotope labeling, NMR and metabolic network modeling to quantify compartmented metabolic fluxes in plants. Metabolic fluxes are the rates of carbon trafficking through various parts of an intracellular metabolic network. We obtained detailed flux maps for two plant systems: soybean embryos and Catharanthus roseus (periwinkle) hairy roots. One of the important breakthroughs of this work is that we were able to quantify fluxes of parallel pathways in separate subcellular compartments, which is essential in plant metabolism but had been challenging to implement.
Postdoctoral
My postdoctoral research focused on investigations of glycerol kinase deficiency, an inherited human disease. We explored metabolic and gene regulatory networks that could be perturbed due to alterations in the levels of the enzyme glycerol kinase.
Current/Future Research: Systems biology and metabolic engineering of higher eukaryotes
Motivation
I am particularly interested in systems biology and metabolic engineering of higher eukaryotes, especially plants and mammalian tissue cultures.
Plants, with their highly sophisticated metabolic architectures, produce numerous essential commodities indispensable to an economy – food, animal feed, fuel, pharmaceuticals, fiber, and feedstocks for the chemical industry – by using just carbon dioxide and sunlight as raw materials. As increasingly larger numbers of plant genomes are now being sequenced, a quantitative understanding of the underlying metabolic and regulatory networks is essential, so that metabolic engineering strategies can be devised for increasing plant productivity.
Two-dimensional [13C, 1H] NMR spectrum of protein hydrolysate from soybean embryos. Metabolic information encoded in these spectra, together with metabolic network modeling and isotopomer balancing, was used to compute carbon flow through metabolic pathways in the embryos. Related Paper »
Mammalian tissue cultures provide a platform to investigate human diseases, thus facilitating the identification of disturbances in biological networks that manifest in a given disease. This can lead to a better understanding of the etiology of the disease and enable improved therapy.
Methodologies
My research objectives are the application and improvement techniques for metabolic flux quantification and metabolic pathway identification, as well as the quantitative reconstruction of gene regulatory networks. This work will involve both experiments and computation. Some techniques that we will utilize are stable isotope labeling, NMR, gas chromatography-mass spectrometry, cDNA microarray analysis, and several computational techniques for metabolic flux/pathway analysis and deduction of regulatory networks.
TopRecent Honors and Awards
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Best Presentation Award, Third International Congress on Plant Metabolomics, 2004.
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Metabolic Engineering III Fellowship, Engineering Conferences International, 2000.
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Best Innovative Potential Master’s Thesis Award, Indian National Academy of Engineering, 1999. Conferred by the Prime Minister of India.
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Young Scientist Award for Best Research Paper, International Congress for Sustainable Development of Environment, 1997.
Selected Recent Publications
Sriram G., Rahib L., He J.-S., Campos A.E., Liao JC, Dipple K.M. (In press, expected 2008) Global metabolic effects of glycerol kinase overexpression in rat hepatoma cells. Molecular Genetics and Metabolism. DOI/Abstract »
Iyer V.V., Sriram G., Fulton D.B., Zhou R., Westgate M.E., Shanks J.V. (In press, expected 2008) Metabolic flux maps: An effective tool for studying the effect of temperature on protein and oil biosynthesis in developing soybean cotyledons. Plant, Cell, and Environment.
Sriram G., Iyer V.V., Fulton D.B., Shanks J.V. (2007) Identification of hexose hydrolysis products in metabolic flux analytes: A case study of levulinic acid in plant protein hydrolysate. Metabolic Engineering 9: 442-451. Cover article. DOI/Abstract »
Sriram G., Fulton D.B., Shanks J.V. (2007) Flux quantification in central carbon metabolism of Catharanthus roseus hairy roots by 13C labeling and comprehensive bondomer balancing. Phytochemistry 68: 2243-2257. Invited, fully peer-reviewed article. DOI/Abstract »
§Sriram G., §González-Rivera O., Shanks J.V. (2006) Determination of biomass composition of Catharanthus roseus hairy roots for metabolic flux analysis. Biotechnology Progress. 22: 1659-1663. [§Contributed equally.] DOI/Abstract »
Sriram G., Martinez J.A., McCabe E.R.B., Liao J.C., Dipple K.M. (2005) Single-gene disorders: What role could moonlighting enzymes play? American Journal of Human Genetics 76: 911-924. DOI/Abstract »
Sriram G., Fulton D.B., Iyer V.V., Peterson J.M., Zhou R., Westgate ME, Spalding M.H., Shanks J.V. (2004) Quantification of compartmented metabolic fluxes in developing soybean embryos by employing biosynthetically directed fractional 13C labeling, two-dimensional [13C, 1H] nuclear magnetic resonance, and comprehensive isotopomer balancing. Plant Physiology 136: 3043-3057. Featured in Faculty of 1000 Biology. DOI/Abstract »
Sriram G., Shanks J.V. (2004) Improvements in metabolic flux analysis using carbon bond labeling experiments: bondomer balancing and Boolean function mapping. Metabolic Engineering 6: 116-132. DOI/Abstract »
Books and Chapters
Sriram G., Application of isotopomer data and mathematical modeling in flux quantification. In: Hanigan M.D., Novotny J.A., Marstaller CL (eds.) "Mathematical Modeling in Nutrition and Health Sciences." Virginia Tech press, Blacksburg, VA. Invited, fully peer-reviewed chapter.
Iyer V.V., Sriram G., Shanks J.V. (2007) Metabolic flux quantification of central carbon metabolism in plant systems. In: Nikolau B.J., Wurtele E.S. (eds.) "Concepts in Plant Metabolomics." Springer. DOI/Abstract. Invited chapter.
Professional Affiliations
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Sigma Xi, The Scientific Research Society
- American Chemical Society
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American Institute of Chemical Engineers (AIChE)
- American Society of Plant Biologists
