A living root bridge near Nongriat village, Meghalaya, India.

(generally considered as an ingenious local bioengineering solution)

Research

How do individual cells process information to make decisions?

Cells transition from one functional state to another and the associated heterogeneity are fundamental to development, disease, differentiation and reprogramming. Cells use molecular networks to sense and process the environmental information to make specific decisions. We are interested in understanding how cells use transcriptional and signaling networks. Our research is driven by twin motivations: to understand the nature and function of networks that cells have evolved; and, apply this knowledge to either control or engineer (reprogram) cells for useful purpose, such as creating better stem cells and driving the cells away from a disease state.

We study pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells. To better elucidate the logic of decision making at individual cell level, we use quantitative single-cell measurements, including single-cell genomics and proteomics. In combinations with experiments, we use computational biology and mathematical modeling to better interpret the data and generate predictive models which can be further verified by experiments.

Malleshaiahlab provides an interdisciplinary collaborative environment to pursue science. The lab members come from diverse fields such as cell biology, computational biology, biochemistry, systems biology, physics and engineering.

We are currently pursuing specific projects focused on the following themes:

  1. Pluripotent stem cell heterogeneity and its significance

  2. Cell state specific configuration and reconfiguration of regulatory networks

  3. Information flow through cell signaling networks

  4. Cellular reprogramming to generate cells with totipotency

  5. Cell type specific regulation of gene expression

 

People

Current members

Thulaj Meharwade, M.Sc.

thulaj.meharwade@ircm.qc.ca

Ph.D. Student, Biochemistry

University of Montreal

Loick Joumier, M.Sc.

loick.joumier@gmail.com

Ph.D. Student, Bioinformatics

University of Montreal

Fariha Anika

fariha.anika@mail.mcgill.ca

B.Sc. Student, Computer Science

McGill University

Melanie Candido

melanie.candido@ircm.qc.ca

Administrative Assistant

Maxime Parisotto, Ph.D.

Maxime.Parisotto@ircm.qc.ca

Research Associate

Mohan Malleshaiah, Ph.D.

mohan.malleshaiah@ircm.qc.ca

Assistant Research Professor

Montreal Clinical Research Institute (IRCM)

Department of Biochemistry and Molecular Medicine

University of Montreal

Alumni

Adrien Sprumont, Master's Student

Current position: Ph.D. student at The University of Oxford, UK.

Loick Joumier, Master's Student

Current position: Ph.D. student at The University of Montreal, Canada.

Abicumaran Uthamacumaran, Intern Student

Current position: B.Sc. Student, Physics, Concordia University, Canada.

 
 

Papers

Trajectory algorithms to infer stem cell fate decisions.

Edroaldo Lummertz da Rocha and Mohan Malleshaiah. 

Computational Stem Cell Biology, Springer Nature (2019). 

 

Reconstruction of complex single-cell trajectories using CellRouter.

Lummertz da Rocha E, Rowe RG, Lundin V, Malleshaiah M, Jha D, Rambo CR, Li H, North TE, Collins JJ, Daley GQ. 

Nature Communications (2018).

 

Hematopoietic Stem and Progenitor Cells from Human Pluripotent Stem Cells.

Sugimura R, Jha DK, Han A, Soria-Valles C, de Rocha EL, Lu YF, Goettel JA, Serrao E, Rowe RG, Malleshaiah M, Wong I, Sousa P, Ditadi A, Keller G, Engelman AN, Snapper SB, Doulatov S, Daley GQ.

Nature (2017).

 

Nac1 Coordinates a Sub-network of Pluripotency Factors to Regulate Embryonic Stem Cell Differentiation.

Malleshaiah M, Padi M, Rué P, Quackenbush J, Martinez-Arias A, Gunawardena J. 

Cell Reports (2016). 

 

Cybernetics, Redux: An Outside-In Strategy for Unraveling Cellular Function.

Malleshaiah M, Gunawardena J. 

Developmental Cell (2016).

 

Real-time protein-fragment complementation assays for studying temporal, spatial and spatiotemporal dynamics of protein–protein interactions in living cells.

Malleshaiah M, Tchekanda E and Michnick SW.

Cold Spring Harbor Laboratory Protocols (2016).

 

In-vivo detection of binary PKA network interactions upon activation of endogenous GPCRs.

Röck R, Bachmann V, Bhang HE, Malleshaiah M, Raffeiner P, Mayrhofer JE, Tschaikner PM, BisterK, Aanstad P, Pomper MG, Michnick SW, Stefan E. 

Scientific Reports (2015).

 

PKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades.

Stefan E, Malleshaiah MK, Breton B, Ear PH, Bachmann V, Beyermann M, Bouvier M, Michnick SW.

Nature Communications (2011). 

 

Protein-fragment complementation assays for large-scale analysis, functional dissection and dynamic studies of protein-protein interactions in living cells. 

Michnick SW., Ear PH., Landry C., Malleshaiah M. and Messier V.

Methods in Molecular Biology (2011)

 

The Ste5 scaffold protein directly controls a switch-like mating decision in yeast.

Malleshaiah M, Shahrezaei V, Swain PS & Michnick SW. 

Nature (2010).

 

A Toolkit of Protein-Fragment Complementation Assays for Studying and Dissecting Large-Scale and Dynamic Protein–Protein Interactions in Living Cells. 

Michnick SW., Ear PH., Landry C., Malleshaiah M. and Messier V.

Methods in Enzymology (2010)

 

A novel genetic screen implicates Elm1 in the inactivation of the yeast transcription factor SBF.

Manderson EN, Malleshaiah M, Michnick SW. 

PLoS One (2008).

Contact

We are constantly looking for talented students and postdoctoral fellows to join our interdisciplinary collaborative team. Interested candidates, with an inclination for quantitative systems biology, should email Mohan Malleshaiah by including a Letter of Interest, full CV and contact information for upto three references.

Inquiries regarding master's and doctoral training should be directed to the following graduate programs:

Department of Biochemistry and Molecular Medicine, University of Montreal.

Molecular Biology, University of Montreal.

Molecular and Cellular Medicine (MCM), IRCM. 

MAILING ADDRESS

Montreal Clinical Research Institute (IRCM)

110 Pine Avenue West,

Room 2750

Montreal, Quebec H2W 1R7

Canada

PHONE NUMBERS

 

Lab Phone                               514-987-5633

Melanie Candido                       514-987-5639

(administrative assistant)

Mohan Malleshaiah Office           514-987-5733

Our research is funded by: