Dr. Matthew Kimber

Dr. Matthew Kimber
Associate Professor
Department of Molecular and Cellular Biology
Phone number: 
52568 / 54590
SSC 2254
SSC 2205


It was clear to me since childhood that I was going to study science, but I ended a structural biologist, as opposed to say, a geologist or astronomer, as much by happenstance as anything else.  While doing a summer undergraduate research project on catalytic RNAs, I became intrigued by the notion that biological macromolecules can be looked at as three-dimensional machines that could, with the right tools, be visualized, prodded, analyzed, taken apart and put back together.  Following this interest led to me entering graduate studies as a crystallographer in the lab of Dr. Emil Pai at the University of Toronto.  After completing my graduate work I elected to forgo the traditional post-doctoral studies, and instead accepted a senior scientist position at a new biotech company in Toronto, Affinium Pharmaceuticals.  Here I used structural biology as a key technology in helping develop new drug candidates, predominantly antimicrobials.  I joined the University of Guelph in 2005.


  • B.Sc. (Hons) Molecular Genetics and Molecular Cell Biology, University of Toronto, 1993
  • Ph.D. Molecular and Medical Genetics, University of Toronto, 2000


Understanding the mechanistic details of how proteins recognize, manipulate and modify other molecules requires detailed knowledge of their structures. In my lab, x-ray crystallography is used as the primary tool to probe the molecular architecture of biological objects; the resulting detailed, three-dimensional models provide the context for interpreting established research findings and generating concrete functional hypothesis. These are then tested using further biochemical experiments to tease out the critical structure-function relationships.

At present, my lab is primarily focused on elucidating the structural organization of bacterial microcompartments, primarily the carboxysome. Carboxysomes are large (90 to 400 nm), polyhedral bodies found in the cytoplasm of cyanobacteria that catalyse the critical reaction that incorporates atmospheric CO2 into nascent sugars. Carboxysomes are made exclusively of protein, with a thin shell which is built from a handful of small proteins by tiling tens of thousands of copies into continuous triangular sheets. The interior core is comprised primarily with the CO2 fixing enzyme, RuBisCO, but also contains several other proteins that mediate a complex network of interactions necessary to structure and organize the body. The carboxysome appears to promote efficient carbon fixation by using its shell to confine CO2 near RuBisCO so that it is fixed, rather than escaping by diffusing through the cellular membranes. Most models of their functioning therefore imply that the shell traps CO2 but allows bicarbonate and other metabolites to pass – i.e. it effectively functions as a selectively permeable, but purely protein, membrane. Above and beyond this effect, the super-molecular organization of this complex possibly results in the emergence of new functional properties that further promote the efficiency of this critical biochemical process. For example, my lab recently showed that the key carbonic anhydrase in the carboxysome, CcmM, is indirectly activated by formation of the shell completion as this protects the enzyme from the reductive environment of the cytosol, allowing disulfide bonds to form. My laboratory is using crystallography to solve the structures of individual carboxysomal components, while in parallel using a variety of techniques to investigate their higher order organization. Ultimately we aim to understand how hundreds of thousands of individual protein chains can interact in a sufficiently controlled manner that an essentially identical object is produced each time.

In addition to this primary research theme, the lab generally has at least a few side projects underway not wholly related to the main research theme; examples include ClpP and its associated proteins (with researchers in Toronto and Cornell), aldolases (with the Seah lab), and proteins involved in LPS maturation and export (with the Whitfield and Lam labs).

Selected Publications

  • Mainprize IL, Bean JD, Bouwman C, Kimber MS, Whitfield C. The UDP-glucose Dehydrogenase of Escherichia coli K-12 Displays Substrate Inhibition by NAD That Is Relieved by Nucleotide Triphosphates. J Biol Chem. 2013; 288(32):23064-74
  • Carere J, McKenna SE, Kimber MS, Seah SY. Characterization of an Aldolase-dehydrogenase complex from the cholesterol degradation pathway of Mycobacterium tuberculosis. Biochemistry. 2013; 52(20):3502–3511
  • Samborska B and Kimber MS. A dodecameric CcmK2 structure suggests ß-carboxysomal shell facets have a double-layered organization. Structure. 2012; 20(8):1353-62.
  • Espie GS, Kimber MS. Carboxysomes: cyanobacterial RubisCO comes in small packages. Photosynth. Res. 2011;109(1-3):7-20.
  • Kimber MS, Yu AYH, Borg M, Chan HS and Houry WA Structural and theoretical studies indicate that the cylindrical protease ClpP samples extended and compact conformations Structure. 2010; 18(7):798-808
  • Peña KL, Castel SE, de Araujo C, Espie GS, Kimber MS. (2010) Structural basis of the oxidative activation of the carboxysomal γ-carbonic anhydrase, CcmM. Proc Natl Acad Sci U S A. 107(6):2455-60.
  • Law AM, Lai SW, Tavares J, Kimber MS. (2009) The structural basis of ß-peptide-specific cleavage by the serine protease cyanophycinase. J Mol Biol.;392(2):393-404.
  • Sun W, Shahinas D, Bonvin J, Hou W, Kimber MS, Turnbull J, Christendat D. (2009) The crystal structure of Aquifex aeolicus prephenate dehydrogenase reveals the mode of tyrosine inhibition. J Biol Chem. 284(19):13223-32.
  • Larue K, Kimber MS, Ford R, Whitfield C. (2009) Biochemical and structural analysis of bacterial O-antigen chain length regulator proteins reveals a conserved quaternary structure. J Biol Chem. 284(11):7395-403.
  • Jørgensen R, Purdy AE, Fieldhouse RJ, Kimber MS, Bartlett DH, Merrill AR. (2008) Cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae. J Biol Chem. 283(16):10671-8.
  • Cuthbertson L, Kimber MS, Whitfield C. (2007) Substrate binding by a bacterial ABC transporter involved in polysaccharide export Proc Natl Acad Sci U S A. 104(49):19529-34.
  • Gribun A, Kimber MS, Ching R, Sprangers R, Fiebig KM, Houry WA. (2005) The ClpP double ring tetradecameric protease exhibits plastic ring-ring interactions, and the N termini of its subunits form flexible loops that are essential for ClpXP and ClpAP complex formation. J Biol Chem. 280(16):16185-96.
  • Kimber MS, Martin F, Lu Y, Houston S, Vedadi M, Dharamsi A, Fiebig KM, Schmid M, Rock CO. (2004) The structure of (3R)-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Pseudomonas aeruginosa. J Biol Chem. 279(50):52593-602.
  • Kimber MS, Vallee F, Houston S, Necakov A, Skarina T, Evdokimova E, Beasley S, Christendat D, Savchenko A, Arrowsmith CH, Vedadi M, Gerstein M, Edwards AM. (2003) Data mining crystallization databases: knowledge-based approaches to optimize protein crystal screens. Proteins. 51(4):562-8.
  • Kimber MS, Nachman J, Cunningham AM, Gish GD, Pawson T, Pai EF. (2000) Structural basis for specificity switching of the Src SH2 domain. Mol Cell. Jun;5(6):1043-9.
  • Kimber MS, Pai EF. (2000) The active site architecture of Pisum sativum β-carbonic anhydrase is a mirror image of that of α-carbonic anhydrases. EMBO J. 19(7):1407-18.


  • MCB*3560 - Structure and Function in Biochemistry
  • MCB*4050 - Protein and Nucleic Acid Structure
  • MCB*6370 - Protein Structure and Bioinformatics

Graduate Students

  • Evan Mallette (M.Sc.)
  • Charles Wroblewski (M.Sc.)

Former lab members

  • Sean White (M.Sc.)
  • Tom Keeling (M.Sc.)
  • Bozena Samborska (M.Sc.)
  • Kerry Peña (M.Sc.)