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Jurgen Sygusch

Analyse structurale des macromolécules et signalisation cellulaire

Professeur titulaire

Faculté de médecine - Département de biochimie et médecine moléculaire

Roger-Gaudry, room D347

514 343-2389

jurgen.sygusch@umontreal.ca

Secondary number: 514 343-6463 (Télécopieur)

Profile

Research expertise

Function of the molecular architecture in enzymatic catalysis, macromolecular interactions and design of inhibitors

To understand how proteins and enzymes function at the molecular level and to translate this knowledge to disease states, we have focused our study on selective macromolecules functioning in metabolism and plant defence. The central metabolic pathway of glycolysis which is found in all living organisms converts glucose to metabolic intermediates that generate energy in form of ATP for cellular functions. The glycolytic enzyme we have studied most intensively is fructose 1,6-bisphosphate aldolase which cleaves a very specific C-C bond that is considered generally difficult to perform chemically. Aldolase has proven to be a rich source of fundamental knowledge on how enzymes perform their catalytic function and is casting a new perspective on the role of glycolysis in various cellular mechanisms. We are examining in particular the role of this enzyme in a number of diseases that involve extensive glucose utilization; these include cancer, protozoan infections (malaria, sleeping sickness, Leishmanias) and type II diabetes. Toxic secondary metabolites are generated during glycolysis which modifies cellular proteins and these modifications have been implicated in a number of pathologies such as diabetes. Deglycation enzymes exist that can undo these types of modifications at the molecular level and are being investigated. Also of interest are related enzymes that cleave the same C-C bond however recognizing substrates that have subtly different substituent geometries about the cleaved bond. Understanding this differential cleavage activity has important application in controlling bacterial virulence. A more recent interest has been the DNA binding activity of plant transcriptional factors to improve plant resistance to disease. The experimental techniques we routinely use to explore biological structure at the molecular level are protein crystallography, molecular dynamics, and enzymology. A long standing interest has been the application of microgravity to protein crystal growth in order to alleviate this bottleneck in crystallographic studies. Protein purification, gene cloning and expression, site directed mutagenesis, enzyme kinetics, bioinformatics and cell culture are also experimental tools we use in our research.

Affiliations and responsabilities

Research affiliations

Teaching and supervision

Student supervision

Theses and dissertation supervision (Papyrus Institutional Repository)

2011

Étude structurale du mode de liaison des protéines Whirly de plantes à l’ADN monocaténaire

Graduate : Cappadocia, Laurent
Cycle : Doctoral
Grade : Ph. D.

Projects

Research projects

2016 - 2022

Structural investigation of reaction intermediates in glycolytic aldolases

Lead researcher : Jurgen Sygusch
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVX20965-(RGP) Programme de subvention à la découverte individuelle ou de groupe
2015 - 2019

Groupe d'étude des protéines membranaires (GEPROM) Cryo-electron microscopy of the bacterial membrane complexes TriABC and MmpL3

Lead researcher : Derek Bowie
Co-researchers : Jurgen Sygusch
Funding sources: FRQS/Fonds de recherche du Québec - Santé (FRSQ)
Grant programs: PVXXXXXX-Subvention de groupe de recherche
2017 - 2018

MmpL3 assays and structure

Lead researcher : Mary Jackson
Co-researchers : Jurgen Sygusch
Funding sources: Bill and Melinda Gates Foundation
Grant programs:
2015 - 2017

ROBOT FOR LIPIDIC CUBIC PHASE (LCP) CRYSTALLIZATION OF MEMBRANE PROTEINS

Lead researcher : Christian Baron
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-(OIR) Outils et d'instruments de recherche (OIR) -1 -(de 7 001 $ à 150 000 $)
2010 - 2016

TRAINING PROGRAM IN CELLULAR DYNAMICS OF MACROMOLECULAR COMPLEXES

Lead researcher : Christian Baron
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PV118026-FONCER : Prog. formation orientée nouveauté, la collaboration et l'expérience en recherche
2005 - 2016

STRUCTURAL INVESTIGATION OF REACTION INTERMEDIATES IN GLYCOLYTIC ALDOLASES

Lead researcher : Jurgen Sygusch
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVX20965-(RGP) Programme de subvention à la découverte individuelle ou de groupe
2012 - 2014

LOW-VOLUME ITC FOR INVESTIGATING BIOMOLECULAR INTERACTIONS

Lead researcher : James G. Omichinski
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-(OIR) Outils et d'instruments de recherche (OIR) -1 -(de 7 001 $ à 150 000 $)
2010 - 2014

PROTEIN SECRETION AND INTRACELLULAR SURVIVAL BY TOXOPLASMA

Lead researcher : David Sibley
Co-researchers : Jurgen Sygusch
Funding sources: NIH/National Institutes of Health (NIH)
Grant programs:
2010 - 2014

STRUCTURAL INVESTIGATION OF REACTION INTERMEDIATES IN GLYCOLYTIC ALDOLASES

Lead researcher : Jurgen Sygusch
2009

MACROMOLECULAR CRYSTALLIZATION FACILITY

Lead researcher : Jurgen Sygusch

Outreach

Publications and presentations

Disciplines

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Areas of expertise

  • Nucleic Acids
  • Biotechnology
  • Cell
  • Combinatorial Chemistry
  • Chromosome (Living Organisms)
  • Inorganic and Organometallic Compounds
  • Enzymes and Proteins
  • Gene (Living Organisms)
  • Macromolecules
  • Biological and Biochemical Mechanisms
  • Bioactive Molecules
  • Organic Molecules and Biomolecules
  • Cell Signaling (Circulatory and Respiratory Health)
  • Chemical Synthesis and Catalysis
  • Biomedical Technologies