Donnelly Centre for Cellular and Biomolecular Research University of Toronto Canada

People

Principal Investigator

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Sachdev Sidhu

Associate Professor

Ph.D. Postdoctoral Fellowship Genentech Inc., South San Francisco
Ph.D. Biochemistry Simon Fraser University, British Columbia
B.Sc. BiochemistrySimon Fraser University, British Columbia

AppointedBanting and Best Department of Medical Research, University of Toronto

Co-investigator Ontario Institute for Cancer Research

Hometown Mission City, British Columbia

Postdoctoral Fellows

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Gang Chen

Post-doctoral Fellow

Ph.D. University of Toronto
M.Sc.East China University of Science and Technology, China
B.Sc.East China University of Science and Technology, China

Research Interests High-throughput approach antibody development

Current Research Currently, my research focuses on deriving antibodies that are capable of neutralizing Staphylococcal Enterotoxin B (SEB). SEB is one of several toxins produced by Staphylococcus aureus and is considered to be one of the primary causative agents of staphylococcal toxic shock syndrome. Through the use of phage-displayed antibody libraries, I hope to develop highly specific SEB-binding antibodies, which could potentially serve as diagnostic tools as well as therapeutic agents against SEB intoxication.

Interests Travelling, skiing, running

Hometown Jiangsu, China

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Andreas Ernst

Post Doctoral Fellow

Ph.D. BiochemistryUniversity of Zürich, Switzerland
M.Sc Chemistry (Dipl.-Ing.)Technical University of Darmstadt, Germany

Research Interests Protein engineering.

Current Research Design of synthetic PDZ variants; selection and design of ubiquitin variants; development of high-throughput methods for phage display, protein expression and purification.

Interests Sports, sailing, reading.

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Haiming Huang

Post-doctoral Fellow

Ph.D. Chinese Academy of Medical Sciences, Peking Union Medical College

Research InterestsProtein-protein interaction, cell signaling pathway, synthetic biology

Current Project 1:Domain-based interactome Protein-protein interaction plays a crucial role in cell signaling, proliferation, cytoskeleton organization, etc.

Many protein-protein interactions are mediated through independently folding modular domains. Those domains, also known as peptide recognition modules, generally recognize and bind to short, linear peptide motifs in their ligands, e.g SH2 and PTB domains associate with phosphotyrosine containing peptide, SH3 and WW domains bind to proline rich motifs. Hence, it is possible to utilize random peptide library to study the binding profiles of protein-protein interaction domains. Using the well established phage display system in our lab, I am trying to define the binding motifs of all the human SH3 and WW domains by a high-throughput screening method. Thus human SH3 and WW interactome maps could be generated through searching protein database by the defined motifs.

Current Project 2: Synthetic protein study We use human SH3 domain of Fyn tyrosine kinase as a model to study the influence of mutations at SH3 domain core on protein folding, binding specificity, thermodynamic stability, etc.

Protein-protein interaction plays a crucial role in cell signaling, proliferation, cytoskeleton organization, etc. Many protein-protein interactions are mediated through independently folding modular domains. Those domains, also known as peptide recognition modules, generally recognize and bind to short, linear peptide motifs in their ligands, e.g SH2 and PTB domains associate with phosphotyrosine containing peptide, SH3 and WW domains bind to proline rich motifs. Hence, it is possible to utilize random peptide library to study the binding profiles of protein-protein interaction domains. Using the well established phage display system in our lab, I am trying to define the binding motifs of all the human SH3 and WW domains by a high-throughput screening method. Thus human SH3 and WW interactome maps could be generated through searching protein database by the defined motifs. We also want to use the human SH3 domain of Fyn tyrosine kinase as a model to study the influence of mutations at SH3 domain core on protein folding, binding specificity, thermodynamic stability, etc.

Birth Country China

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Helena Persson

Postdoctoral Fellow

Ph.D. Immunotechnology Lund University, Sweden
M.Sc. Biomolecular Engineering Uppsala University, Sweden

Research Interests Antibody generation and evolution

Current Research My postdoc project involves development of synthetic antibody libraries as source of tools for research, diagnostic and potential therapeutics. I also use these repertoires to explore basic aspects of antibody-antigen recognition.

Interests Travelling, skiing, running.

Hometown Uppsala, Sweden

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Graduate Students

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Nishant Chakravorty

Interning Graduate Student

Masters in Medical Science & Technology (MMST) Indian Institute of Technology, Kharagpur, India
MBBS Patna Medical College, Patna, India

Research Interests Human genetics and proteomics.
I have always been fascinated by the structure of the human genome and the wonders it achieves. This fascination made me interested in research in the field of human genetics and proteomics.

Current Research Specificity profiling of PDZ domains.
I am presently working on a project involving specificity profiling of the PDZ domain. I am interning at the Sidhu lab as part of my final year project at the Indian Institute of Technology.

Long Term Research Goals Human genetics research: gene re-activation, gene induction.

My long term research interest is to work in the area of gene manipulation and re-activation; specifically of certain genes that are silenced during the human fetal life. I believe that such a break-through will prove to have immense clinical benefits in certain conditions that currently remain incurable

Interests Reading books, listening to music. I also enjoy playing cricket.

Hometown Dhanbad, India

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Nicolas Economopoulos

Graduate Student

B.Sc. Honours Molecular Genetics and Microbiology SpecialistUniversity of Toronto

Research InterestsAntibody engineering, cell signaling

Current Research Developing a high-throughput system of antibody-phage display that allows for the large-scale targeting of cell signaling pathways.

My goal is to use the versatility of antibody scaffolds and the combinatorial power of phage display libraries to develop a high-throughput system that allows for the large-scale targeting of intracellular pathways. The realization of such a system will enable researchers to simultaneously investigate a wide array of biological questions without the current constraints imposed by antibody structure, the intracellular environment and experimental scale.

InterestsMartial Arts (especially Brazilian Jiu-Jitsu), music (composing and playing), reading, board games, working out.

Hometown Toronto, Canada

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Megan McLaughlin

Graduate Student

B.Sc. Genetics University of British Columbia
B.Sc. Honours Genetics University of British Columbia

Current Research My project is based on PDZ domains, which are protein-protein interaction domains that bind the C-terminus of other proteins. There are over 250 PDZ domains in the human genome, located in more than 100 proteins, and these domains interact with specific ligands to assemble a variety of defined protein complexes.

One of the goals of my project is to improve our understanding of specificity in protein-protein interactions using PDZ domains as a model system. We use combinatorial libraries to generate comprehensive data sets that can also be used to improve computational methods of predicting specificity.

The second goal of my project is to exploit the peptide-binding function of PDZ domains by converting them into affinity reagents that can be used inside living cells. Beyond the usual uses of affinity reagents (eg. immunoprecipitation, Western blots and immunofluorescence), PDZ-based affinity reagents could be used to change the localization of a ligand, to outcompete an interaction with a natural PDZ domain or to create scaffolding proteins that assemble novel protein complexes. We anticipate that these PDZ-based affinity reagents will be particularly useful tools for studying signal transduction, but they could be used to study nearly any facet of cell biology.

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Javier Murciano-Calles

Graduate Student

B.Sc. Chemistry University of Granada, Spain

Research Interests Protein folding, protein-ligand interaction.

Current Research Thermodynamic and structural analysis of the stability of PDZ domains and their interactions with peptide ligands. Rational designing of new therapeutic ligands.

PDZ domains have a well defined topological pattern in terms of content and distribution of their secondary structure elements. Previous studies carried out with other small sized proteins clearly indicate the determinant role of this pattern in the folding mechanism.

Although the relevance of the conformational properties of the interactions of modular domains with their ligands has always been presumed, the lack of a correct understanding of the energetic and structural factors make it necessary to achieve in-depth biophysical characterization of these biological systems.

Another approach to advance in the understanding of the molecular basis of interactions between PDZ domains and their ligands is what I am carrying out in the Sidhu Lab by using phage display. The plan is to generate libraries with up to billions of variants and establish which of these are the most specific to different targets. Afterwards, the structural and thermodynamic characterization of these interactions will allow the rational designing of novel ligands as potential drugs.

Interests Soccer, basketball, hiking, reading, talking with friends.

Hometown Úbeda, Spain

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Raffi Tonikian

Graduate Student

B.Sc. Chemistry and Biochemistry Concordia University

Research Peptide recognition modules (PRMs) mediate many protein-protein interactions required for the assembly of biological complexes and pathways. The fidelity of these interactions in a spatially and temporally controlled fashion is an underlying feature of cellular life; consequently, aberrant interactions often result in abnormal cellular behaviour and disease (Pawson and Nash, 2003).

I am using phage-displayed peptide libraries to query the binding specificities of two common PRMs, namely the SH3 and PDZ domain. Understanding the molecular determinants of binding to these domains will allow for improved binding specificity and interaction networks predictions, which will help illuminate the cellular circuitry underlying signal transduction pathways required for normal and disease cell states.

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Technicians

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Linda Beatty

Technician

B.Sc. HonoursYork University

Research InterestsI'm relatively new to phage display but am genuinely excited about the huge potential of this technique.

Current Research Using phage display to find variants of ubiquitin with enhanced binding to proteins involved in ubiquitylation and deubiquitylation pathways.

After graduating from York University, I began my scientific career in Paul Sadowski’s lab in the Dept. of Medical Genetics here at U of T, back in the days when we made our own restriction enzymes, mouth pipetted everything and smoking in the lab was commonplace.

I worked first on bacteriophage T7, then on the FLP recombinase from yeast 2 micron circle and finally on aspects of human genomic imprinting.

Decades later in the Sidhu Lab I have come full circle and again work with bacteriophage, but as a tool instead of an organism of study.

I still have to resist the urge to mouth pipette and the only smoke in the lab lately has been from when I tried to set fire to the microwave.

Long Term Reserach Goals Figuring out how to use a Mac computer.

Linda Beatty sailing

InterestsBoats, Beaches, Bars and Ballads. (This is the name of singer Jimmy Buffett's box set but happens to describe many of my interests quite well.)

Hometown Toronto, Canada

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Nick Jarvik

Technician

B.A.University of Toronto
History and Philosophy of Science (major)
Biology, Political Science (minor)

Research InterestsSPR, liquid handling and colony picking robots, growing cells.

Current Research Affinity measurement by SPR, expression and purification of affinity reagents and antigens.

InterestsMusic and general lounging.

Hometown Pittsburgh, USA

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Alevtina Pavlenco

Technician

M.Sc. BiologyInstitute of Ecological Genetics, Academy of Sciences, Moldova

Research Interests New applications of antibody in research and medicine. Affinity reagents development.

Current Research Antibody phage display against various targets.

Interests Reading, travelling, dancing.

Hometown Chisinau, Moldova

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Wei Ye

Technician

B.Sc. Genetics Fudan University, Shanghai, China

Current Research I work with Helena on constructing synthetic antibody libraries and selecting specific Fabs for different protein targets using the phage display system.

Now I am very sensitive to the numbers 96 and 384 due to the high-thoughput method of phage display selection and phage ELISA and always feel excited when waiting for the samples to turn blue after adding ELISA substrate.

Interests I like the scientific environment and the international culture in the Sidhu Lab.

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Interns

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Pankaj Garg

Summer Intern

B.Sc. Biotechnology HonoursUniversity of British Columbia
Diploma of Technology in Biotechnology, HonoursBritish Columbia Institiute of Technology

Research InterestsAnything protein related interests me.

Current Research Crystallization screens of PDZ Constructs. Designing a lentiviral vector to display C-terminal peptides in mammalian cell lines. Phage Display.

Long Term GoalsGet a Ph.D. in biotechnology

InterestsWorking out - working hard towards getting a six-pack. The pubs in Toronto are working against it. Travel - the next two places on my list are Thailand and Amsterdam.

Hometown Born in Kanpur, India. Raised in Ferozepur, India. Studied in Shimla, India.

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Gavneet Sandhu

Summer Intern

B. Sc. University of Toronto (2nd year)

Research Interests Gene therapy

Current Research Indentify human SH3 binding profiles.

InterestsMovies and music, poker and chips.

Hometown Gurgaon, India

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Amit Singh Kainth

Summer Intern

B.Sc. BiochemistryUniversity of British Columbia

Research InterestsProteomics research, specifically protein- protein interactions.

Current Research Utilizing the yeast two-hybrid screen to identify SUMO (small ubiquitin-related modifier) interacting partners in Saccharomyces cerevisiae. Protein purification.

InterestsSports! Play a lot of ice hockey and soccer. The Vancouver Canucks!! Traveling with friends and family.

Hometown Vancouver, British Columbia

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Irina Sochirca

Summer Intern

B.Sc. Cell and Molecular Biology SpecialistUniversity of Toronto

Research Interests I find all areas of research fascinating, including the everyday challenges and the rewards of discovery.

Current Research Making full length IgG. Kunkel mutagenesis.

Hometown Chisinau, Moldova

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Last Modified 8 December, 2009 12:46 PM