University of Toronto, Faculty of Applied Science & Engineering

Chemical Engineering & Applied Chemistry

Radhakrishnan Mahadevan

R Mahadevan

B.Tech. (Indian Institute of Technology), Ph.D. (Delaware)

Principal Investigator, Laboratory for Metabolic Systems Engineering  and
BioZone - Centre for Applied Bioscience and Bioengineering

Room: WB326 | Tel.: 416-946-0996 | Email: krishna.mahadevan@utoronto.ca


 

Memberships

American Institute of Chemical Engineering
American Chemical Society
American Society for Microbiology
Biophysical Society

Research Interests

Systems Analysis and Engineering of Biological Processes

Research Interests: modeling and analysis of metabolic and regulatory networks, bioinformatics and systems biology, engineering biological systems for applications in metabolic engineering, bioremediation, bioenergy and bioprocess optimization.

Recent advances in experimental and computational technologies have enabled the detailed characterization of biological systems. In particular, the molecular components of these systems including the list of genes, proteins they encode, and compounds that interact with these proteins can be determined. This availability of tools to analyze system-wide changes at the level of the genes, proteins, and metabolites has created significant opportunities to understand cellular functions, and to ultimately design processes in a systematic way for applications in industrial and medical biotechnology (e.g. metabolic engineering, bioprocess optimization and control). The research interests of our group involve the development and utilization of dynamic mathematical models of biological systems for improved design, optimization and control.

Genome-scale models of cellular processes

Although detailed models of cellular processes have been constructed in the past, research in this area has attained a new dimension in the last few years due to the development of novel high-throughput experimental techniques for both sensing and manipulating cellular processes at a molecular level. As an example, both steady state genome scale models and smaller dynamic models of metabolism of several industrially important organisms including Escherichia coli have been developed in the past. More recently, such models have been developed for a metal reducing bacteria (Geobacter sulfurreducens) with applications in bioelectricity and bioremediation and have been used to rationally engineer the metabolism for improved electricity generation. However, further research is required to extend such models of metabolism to represent the inherent dynamics of biological systems and to account for the increased complexity in multi-cellular organisms and microbial communities.

Metabolic Engineering using Systems and Synthetic Biology

Availability of genome-scale metabolic models can accelerate the optimization of metabolism for the synthesis of biochemicals and fuels. A key requirement for sustainable development is the ability to synthesis chemicals and fuels from renewable feedstocks. We are using these genome-scale models to optimize microbial metabolism for the production of fuels and chemicals. In addition, we are also develop novel synthetic biology tools using genetic circuits such as toggle switch for the dynamic control of metabolic pathways in order to optimize metabolism effectively for biochemicals production.

Optimization and control of biological processes

Several engineering disciplines (e.g., mechanical, electrical, & chemical) routinely use quantitative models for design and optimization of processes of interest. However, such rational approach to design and optimization has been possible in the life science only recently due to the lack of predictive large-scale models of biological processes in the past. Research activities in our group include the design of dynamic model-driven engineering strategies for biological process optimization and control across different length and time scales (i.e., from microscopic (intracellular) processes to macroscopic (bioreactor) processes). Applications can include metabolic engineering (e.g., increasing the rate of electrical current in microbial fuel cells, designing dynamic gene manipulation strategies for increased product yields), biomedical engineering (drug design and dosage, personalized nutrition and medicine), bioreactor control and optimization (designing optimal substrate and inducer feeding strategies), and bioremediation (determining the spatiotemporal substrate addition strategies to effectively stimulate microbial activity).

Selected Publications

Gawand P, Hyland P, Ekins A, Martin VJ, Mahadevan R. Novel approach to engineer strains for simultaneous sugar utilization. 2013,  Metab Eng. 20, 63-72.

N. Anesiadis, H.Kobayashi, W. R. Cluett, R. Mahadevan, “Analysis and design of a genetic circuit for dynamic metabolic engineering”, 2013, ACS Synthetic Biology, 2(8):442-52.

T. Khaezei, A. McGuigan, R. Mahadevan, “Ensemble Modeling of Cancer Metabolism”, 2012, 3,1-14, Frontiers in Computational Physiology and Medicine.

K. Zhuang, G. Vemuri, R. Mahadevan*, “Economics of Membrane Occupancy and Respiro-fermentation”. 2011, 7:500, Nature Groups’ Molecular Systems Biology.

R. Mahadevan*, B. O. Palsson, and D. R. Lovley, “In situ to in silico and back: elucidating the physiology and ecology of Geobacter spp. using genome-scale modelling”, Nature Reviews Microbiology, 2011, 9(1), 39-50. (Featured on the cover page)

K. Zhuang, C. Risso, M. Izallalen, H. Richter, P. Mouser, R. Mahadevan, and D. R. Lovley, “Genome-Scale Dynamic Modeling of Competition among Rhodoferax and Geobacter in anoxic environments”, Nature Groups’ ISME Journal, 2010, 107, 352.

(*:  corresponding author)

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