Mads Kaern

 
Degrees

B.Sc., University of Copenhagen, 1995
Cand. Scient., University of Copenhagen, 1997
Ph.D., University of Toronto, 2001

Biography

Dr. Kaern received his B.Sc. (1995) and M.Sc. (1997) from the University of Copenhagen. His M.Sc. thesis entitled “Biochemical Reaction Networks: From Elementary Reactions to Biological Self-organization” resulted in three research publications in theoretical biology, and received the rarely awarded and highest possible grade of 13 for “outstanding and exceptional performance”. Dr. Kaern was a doctoral stipendiary with the Danish Research Academy from 1997 to 2000, and completed his Ph.D. research on chemical and biological morphogenesis at the University of Toronto in 2001. As a postdoctoral fellow of the Danish Research agency, he then went to Boston University’s Department of Biomedical Engineering working with McArthur “Genius” Award recipient Dr. James Collins and National Academy of Science members Dr. Nancy Kopell and Dr. Charles Cantor. Dr. Kaern was appointed Canada Research Chair in Systems Biology in 2004. He is a core member of the Ottawa Institute of Systems Biology, and an Assistant Professor of Cellular & Molecular Medicine with cross-appointment in the Department of Physics at the University of Ottawa. He launched his Dynamical Systems Biology Laboratory and independent research program in 2005.

Dr. Kaern is a promising young scientist and biotechnology innovator. In his short career, he has authored over 20 scientific publications collectively cited more than 500 times and holds one biotechnology patent as a co-inventor. He was a leading initiator behind the Canadian Society for System Biology and was elected Founding President of this society. Ottawa Life Magazine named him among the “Top 50 People in the Capital” in 2005. With expertise in genetic engineering, dynamical systems theory and computational modelling, Dr. Kaern focuses on complex gene regulatory processes. This research aims at understanding fundamental properties governing cellular signal processing and transduction to facilitate advances in biotechnology, biopharmaceutical and biomedicine, including stem cell research and studies of multifaceted disease. His research is funded by the Canadian Institutes of Health Research; the National Science and Engineering Research Council; the Canadian Foundation for Innovation; the Canadian Research Chair Program; Ontario’s Ministry of Economic Development and Trade; and the University of Ottawa.

Research Projects

• Genetic network engineering. The mapping of molecular interactions in living cells has provided critical information about the gene networks that regulate cellular functions and contribute to disease. However, these mapped networks are often too complex to allow us to infer or predict the systems-level properties of genome regulation. To address this, we combine genetic engineering, computational biology and dynamical systems theory and create synthetic gene regulatory networks in yeast that simulate control of cell signal processing and transduction. The goal is to improve our understanding of network function and design, and our ability to engineer gene networks with complex properties for biotechnological applications.

• Impact of stochasticity in gene expression on fitness and adaptation. It has been hypothesized that variability in gene expression may improve the fitness of cell populations experiencing acute stress. This is supported by the observation that the expression of stress-related genes is more “noisy” than other genes. To determine how gene expression noise impacts population fitness, we have designed a synthetic genetic cascade in yeast to map the correlation between environmental stress, gene expression noise and population fitness. We use this system to expand on the "noisy" stress-gene hypothesis and develop computational tools for analyzing linkages between gene regulatory and population dynamics.

• Design principles of gene regulatory networks. The mapping of gene regulatory networks have revealed that most of these networks involves complex systems-level features, such as multi-layered feedback control. It has been hypothesized that this complexity reflects an evolutionary optimization conferring the network with functional robustness to internal and external perturbations. To investigate how network architecture impacts network function and robustness, we employ a combination of experimental and computational approaches. In our experimental studies, we use gene-substitution schemes, high-resolution phenotyping and quantification methods in yeast to investigate the effect of gene dosage on adaptation and response to external perturbations (i.e., change in nutrients or stress-inducing agents). In our computational studies, we are developing new computational methods to quantify robustness, and to determine who specific network features contribute to network function. This research is conducted in the context of the human embryonic stem cell switch controlling the transition from self-renewal and pluripotency to lineage commitment and differentiation.

• Development of a bioinformatics platform to annotate, integrate, analyze and visualize cell regulatory networks. The introduction of high-throughput methods have rapidly accelerated the accumulation of data regarding the molecular interactions networks (the interactome) controlling how gene expression states (the transcriptome) change as cells transition from one state to another. We are developing and implementing an innovative bioinformatics workbench that can be used to consolidate and derive new biological knowledge from the continuously expanding body of experimental evidence. A particular emphasis of our work is tools for integrative networks analysis in stem cell research where different types of interactions (e.g., protein-protein and protein-DNA interactions) and different types of pathways (e.g., core regulatory processes and signal transduction pathways) are seamlessly integrated with genomics information (e.g., gene annotations, gene sequences and cis-regulatory elements) and time- and context-dependent abundance data (e.g., gene expression microarrays). The goal is to enable stem cell researchers to annotate, analyze and visualize information about embryonic and adult stem cells function, lineage determination and differentiation, and facilitate new bioinformatics discoveries, including the development of models describing these processes, by computational biologists.

Research Productivity

TEN MOST CITED CONTRIBUTIONS*

191 Nature, 422, 633-637 (2003). 89 Nature Reviews Genetics 6, 451-464 (2005). 51 Proceedings of the National Academy of Science U.S.A. 22, 8418-8419 (2004). 46 Physical Review E 60, R3471-3474 (1999). 24 Journal of Theoretical Biology 207, 473-493 (2000). 22 Annual Reviews in Biomedical Engineering 5, 179-206 (2003). 17 Faraday Discussions 120, 295-312 (2001). 16 Physical Review E 61, 3334-3338 (2000). 14 Biophysical Chemistry 87, 121-126 (2000). 12 Journal of Physical Chemistry A 106, 4897-4903 (2002).

*Based on the ISI web of science database, January 26, 2007

• Co-inventor. Engineered Enzymatically Active Bacteriophages and Methods of uses Thereof. James J. Collins et al. PCT/US2005/032365 (2005).

• Keynote presenter. Alberta Integrated Life Sciences Workshop. Banff. February 2006.
• Invited Speaker. Centre for Genome Regulation, Barcelona. December 2006. Symposium on Systems Biology: A cell in the computer?
• Invited Speaker. Laval University. October 2006. CREFSIP Seminar.
• Invited Lecturer. McGill University. May 2006. Systems Biology Summer school.
• Invited Speaker. University of Ottawa. May 2006. Applied Mathematics Seminar
• Invited Speaker. McGill University. April 2006. Centre for Bioinformatics Seminar
• Invited Speaker. University of Ottawa. April 2006. OISB Science Retreat
• Invited Speaker. Mount Tremblant. March 2006. CIAR Conference.
• Invited speaker. National Research Council, Ottawa. November 2005. Ottawa Institute for Systems Biology Annual Symposium.
• Invited speaker. University of Guelph. July 2005. DCDIS 4th International Conference.
• Invited speaker. Keystone Symposia. Keystone. Colorado. April 2005. Systems and Biology.
• Invited speaker. Banff. Alberta. March 2005. Society for Biochemistry, Molecular and Cellular Biology Annual Meeting
• Invited speaker. Philadelphia. October 2004. Biomedical Engineering Society Annual Fall Meeting.
• Invited speaker. Braunschweig, Germany. October 2004. Workshop on Complexity and fragility of cellular networks.
• Invited lecturer. Heidelberg, Germany. October 2004. 5th International Conference on Systems Biology (ICSB).
• Invited speaker. Winnipeg. June 2004. Canadian Association of Physics Conference.
• Invited lecturer. Washington University, Saint Louis. November 2003. 4th ICSB.
• Keynote presenter. Karolinska Institute. December 2002. 3rd ICSB.
• Invited speaker. University of Notre Dame. August 2002. 15th International Symposium on Mathematical Theory of Networks and Systems.
• Invited contributor. Faraday Discussion 120. Nonlinear Chemical Kinetics: Complex Dynamics and Spatiotemporal Patterns. University of Manchester. September 2001.
• Invited speaker. NATO Advanced Research Workshop: The Origin and Fate of Somites. University College London. August 2000.
• Invited speaker. The Gordon Research Conference on Oscillations and Instabilities in Chemical Systems. Roger Williams University. August 2000.
• Invited speaker. Symposium on Nonlinear Dynamics in Biology. Niels Bohr Institute, University of Copenhagen. May 2000.

• Editorial Board Member. Systems and Synthetic Biology.
• Co-organizer. EOI for Integrative Systems Biology as Genome Canada Research Theme.
• Steering Committee Member. The Canadian Society for Systems Biology.
• Hiring Committee Member. The Ottawa Institute for Systems Biology.
• Co-organizer. The Ottawa Institute for Systems Biology Annual Symposium (2006).
• Organizer. The Inaugural Meeting of the Canadian Society for Systems Biology (2006).
• Organizer. Computational Regulomics Workshop. Sprott Centre for Stem Cell Research (2006).
• Organizer and co-applicant. NSERC training program in Computational Regulomics for the CFI International Joint Venture Application "The International Regulome Concortium".
• Named “Top 50 People in the Capital” by Ottawa Life Magazine (2006).
• Invited Participant. Canadian Institutes of Health Research workshop Integrating the Physical and Applied Sciences into Biomedical Research II (2006).
• Co-organizer. Workshop on Integrative Systems Biology in Canada. Terrence Donnelly Centre for Cellular & Biomolecular Research. University of Toronto (2006).
• Founding President. The Canadian Society for Systems Biology (2005/2006).
• Invited Participant. Mathematics Workshop for the U.S. Department of Energy’s Genomes to Life Program (2002).