Shireesh Srivastava

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Shireesh Srivastava – PhD

Group Leader- Systems Biology & Biofuel
Integrative Biology Group
International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg,110 067 New Delhi, India.
E-mail: shireesh@icgeb.res.in
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Education
  • Michigan State University, East Lansing, MI, USA, PhD (Chemical Engineering), 2007
  • Indian Institute of Science, Bangalore, KA, India, MSc (Eng.), Chemical Engineering, 2001
  • Devi Ahilya University, Indore, MP, India, MSc (Biotechnology),1999
Career History
  • Since 2012, Team Leader, DBT-ICGEB Center for Advanced Bioenergy Research, New Delhi, India
  • 2007-2012, Postdoctoral Visiting Fellow, Laboratory of Metabolic Control, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Rockville, MD, USA
  • 2002-2007, Research Assistant, Department of Chemical Engineering, Michigan State University, East Lansing, MI, USA
Research Interests

Systems biology, Metabolic engineering, Flux Balance Analysis, Metabolic flux analysis, Cyanobacterial biotechnology, Metabolic labeling studies, Bioprocess Technology

Research Description

Flux balance analysis (FBA) and
Metabolic flux analysis (MFA) to identify gene targets and the effects of manipulations

FBA and MFA are two tools of metabolic engineering that help analyze the distribution of fluxes through various intracellular pathways. FBA can provide information on the metabolic space of organisms, i.e., it can model the metabolic response of organism, such as the response to various carbon sources as well as growth under different conditions. FBA can also model the effects of gene modifications, e.g., deletion of genes or addition of heterologous pathways (a.k.a. synthetic biology) on parameters of interest such as growth rate and product formation rate. Such information helps in identifying the optimal targets for genetic manipulation to engineer cellular metabolism in desired direction(s). FBA is applied to either genome-scale metabolic models or models of core metabolic networks in order to glean information about cellular metabolic responses. Metabolic flux analysis (MFA) is applied to identify the effects of gene modification on the distribution of intracellular fluxes under specific conditions.

Systems biology to increase biofuel production
Systems biology is the study of biological system from a global viewpoint. The development of omics technologies has made it possible to analyze biological systems on global scales. This leads to a plethora of data that must be analyzed efficiently, and correctly, so as to gain insights into the specific biological networks. As biological systems are interrelated networks of genome, transcriptome, metabolome and proteomes, the response of biological systems to environmental and genetic manipulations is always complex. Understanding the inter-relationships between the different –omes is critical to simulate the cellular response to manipulations. We apply various systems biology techniques to integrate high throughput data in order to understand cellular responses to stresses and also the pathways and processes associated with lipid and fuel alcohol production. These techniques also help in identifying targets for optimizing biofuel production.

Scientific Activity

Research in my lab involves applying the methods and skills of metabolic systems biology to optimize growth rate and biofuel production of diverse microorganisms. We supplement experiments with modeling approaches in order to streamline discovery and optimization. This includes application of flux balance analysis (FBA) and metabolic flux analysis (MFA) to identify the intracellular distribution of metabolic fluxes and identify the targets for further manipulation. The predictions of metabolic modeling are verified experimentally. This approach is being investigated in various microorganisms, including, but not limited to, native isolates of cyanobacteria. Additionally, traditional metabolic engineering (knock-out and overexpression of genes) as well as synthetic biology approaches (introduction of optimized heterologous pathways) are being employed in cyanobacteria to make diverse products including biofuels.

Previous research involved investigated various aspects of lipid biochemistry and metabolism at enzyme, cell culture and whole animal level. This included investigating the synthesis of flavor esters in supercritical CO2 by investigating lipase catalyzed esterification in this novel medium. I have also applied systems biology framework (integration of various high throughput data) to identify the mechanisms of toxicity of saturated free fatty acids to human hepatoma cells, as well as in vivo studies on the effect of ketone bodies (a product of FFA oxidation) on whole animal physiology and specifically on brown fat in mice.

Publications
  • Desai T, Srivastava S. Constraints-Based Modeling to Identify Gene Targets for Overproduction of Ethanol by Escherichia coli: The Effect of Glucose Phosphorylation Reaction. Metabolomics 2015;5: 145. doi:10.4172/21530769.1000145.
  • Kemper MF, Srivastava S, King MT, Clarke K, Veech RL, Pawlosky RJ. An Ester of β-Hydroxybutyrate Regulates Cholesterol Biosynthesis in Rats and Cholesterol Biomarker in Humans. Lipids. Accepted Oct 2015.
  • Srivastava S, Veech RL. Ketogenic diet elevates mitochondrial proteins and UCP1 in mice. IUBMB Life. 2013 Jan;65(1):58-66. doi: 10.1002/iub.1102. Epub 2012 Dec 10. Erratum in: IUBMB Life. 2014 Jul;66(7):519.
  • Srivastava, S., Kashiwaya, Y., King, M.T., Baxa, U., Tam, J., Niu, G., Chen, X., Clarke, K., Veech, R.L. 2012. Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet. FASEB J 26, 2351-2362
  • Srivastava, S., Chan, C. 2008. Application of metabolic flux analysis to identify the mechanisms of free fatty acid toxicity to human hepatoma cell line. Biotechnol Bioeng 99, 399-410
  • Srivastava, S., Zhang, L., Jin, R., Chan, C. 2008. A novel method incorporating gene ontology information for unsupervised clustering and feature selection. PLoS ONE 3, e3860
  • Srivastava, S., Li, Z., Yang, X., Yedwabnick, M., Shaw, S., Chan, C. 2007. Identification of genes that regulate multiple cellular processes/responses in the context of lipotoxicity to hepatoma cells. BMC Genomics 9, 364
Books
  • Desai TS, Dutt V, Srivastava S. Systems biology and metabolic engineering of cyanobacteria for biofuel production. In: Marine Bioenergy: Trends and Developments, Se-Kwon Kim (Ed), CRC Press 2015; 163–178. DOI: 10.1201/b18494-13.
  • Srivastava S, Li Z, Chan C. Identification of gene-networks associated with cell-death in lipotoxicity. Methods in Molecular Biology: Caspase Regulation. 2010. Ed. Jeffrey Varner.
  • Chan C, Li Z, Srivastava S. Integration of Micro-Array and Metabolic Data. Mathematical Modeling in Nutrition and Agriculture. 2007; Chapter 5: p 82-96. Ed. Mark Hanigan.

GROUP MEMBERS

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Preeti Rai – PhD

Post-doc Fellow
E-mail : rai_preeti02@yahoo.co.in.
Area of work: Genetic engineering of Cyanobacteria, Protein isolation, purification and characterization, Molecular Biology, Cotton tissue culture and transformation.

Pathway engineering of marine cyanobacteria Synechococcus PCC 7002, for the increase in glycogen production.

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Desai Trunil Shamrao – M. Tech.PhD student

E-mail : trunil@icgeb.res.in.
Hobby: Hiking, Learning about ecosystems.
Area of work: Systems Biology.My work involves design and implementation of engineering strategies in the marine cyanobacterium Synechococcus sp. PCC 7002 for production of biofuel molecules.

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VAISHALI DUTT – M.Sc.PhD Student

E-mail : duttvaishali54@yahoo.com.
Hobby: READING.
Area of work: BIOFUEL PRODUCTION FROM CYANOBACTERIA.My research involves engineering cyanobacteria for production of biofuel candidates and then optimizing the titers by manipulating the culture conditions.

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Ahmad – M.Sc.

JUNIOR RESEARCH FELLOW
E-mail : ahmadbioinfo@gmail.com.
Hobby: Exploring Historic Places.
Area of work: Metabolic Modeling and Systems Biology.My research involves reconstructing genome scale metabolic models. I apply Flux Balance Analysis-based methods to analyze these models in order to gain insights into organism behavior under different conditions, and identify suitable targets to produce desired products.

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Ruchi Pathania – M.Sc. (Biochemistry)

PhD Student
E-mail : rpathania@icgeb.res.in.
Hobby: Reading books, Listening music
Area of work: Cyanobacterial engineering.Working on nitrogen fixation pathway in marine Cyanobacteria

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Jai Kumar Gupta – M.Sc. (Biotechnology)

PhD Student
E-mail : jkgupta@icgeb.res.in.
Hobby: Helping needy children
Area of work: Cyanobacterial engineeringMy current project is to improve carbon di oxide transport in Cyanobacteria.

Careers at ICGEB

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