Jia | Biomedical and Molecular Sciences | School of Medicine

Zongchao Jia PhD

Position(s)

Professor

Tier 1 Canada Research Chair

Contact Info

jia@queensu.ca

613-533-6277

Bottorell Hall, Room 626

Jia Lab Website: www.queensu.ca/protein-lab

Faculty Bio

Dr. Zongchao Jia is a Professor of Biochemistry and Tier 1 Canada Research Chair in the Department of Biomedical and Molecular Sciences, Queen’s University. Prior to joining Queen's in 1995, he obtained Ph.D. from University of Saskatchewan and received post-doctoral training in University of Oxford, focusing on structural biology studies of protein phosphorylation and function implications. He progressed to the rank of Full Professor in 2004 and holds Canada Research Chair since 2000. Dr. Jia has had extensive experience in protein structure-function studies. In particular, he has been actively involved in researching protein phosphorylation and protein modification by polyphosphate, newly discovered in Jia lab, calcium-binding proteins, host-pathogen interactions, and structure-based drug design. As a very active and productive researcher, he has published 300 papers, including 8 in Nature, Science and Cell. His work has been cited >14,000 times, with H index of 56. In addition, he has several patents. His achievement has been widely recognized, receiving numerous awards including Queen’s National Scholar, Medical Research Council Scholar, Ontario Premier Research Excellence Award, Queen’s Basmajian Award for Excellence in Medical Research, Queen’s Chancellor’s Research Award, Canadian Institutes of Health Research Investigator, Natural Sciences and Engineering Research Council of Canada Steacie Fellow, Queen’s Award for Excellence in Research, Killam Fellow etc.

Research Interests

Protein phosphorylation, the attachment of a single phosphate group to specific amino acids, has long been recognized as one of the most studied post-translational modifications (PTMs). Phosphorylation plays a critical role in regulating protein function, signaling pathways, and cellular processes. However, a novel and emerging class of modifications, termed protein polyphosphate modifications (PPM), has been recently identified and offers a fascinating new layer of regulation in protein biology.

PPM involves the attachment of polyphosphate (polyP)—an inorganic polymer made of many phosphate units—to proteins. PolyP is evolutionarily conserved and found in organisms across all domains of life. While its synthesis and regulatory functions are well characterized in prokaryotes and simpler eukaryotes like yeast, much about its origin, regulation, and roles in higher eukaryotes remains largely unknown.

Our lab has made exciting advances in this area, revealing a previously unknown interaction in which proteins with histidine repeats exhibit a high affinity for polyP. This interaction leads to a non-covalent modification, which we have termed histidine-polyphosphate modification (HPM). Although the interaction is not covalent, it has significant implications for protein function, altering protein activity and possibly regulating cellular processes. This discovery opens up new avenues for understanding how polyP contributes to cellular regulation.

In addition to HPM, we have identified consecutive lysine-polyphosphate modification (KPM). Like HPM, KPM arises from ionic interactions, where polyP binds to lysine-rich clusters of proteins, potentially influencing their behavior. Together, these two forms of PPM represent a novel class of ionic post-translational modifications, with the potential to regulate a wide range of protein functions, including protein-protein interactions, subcellular localization, and enzymatic activity.

Our ongoing research aims to deepen our understanding of these polyphosphate-mediated modifications and their biological significance. Our main objectives include:

Screening for PolyP-Modified Proteins: We are developing techniques to identify proteins that undergo polyphosphate modification across various species, with a particular focus on eukaryotic cells.
Characterizing PolyP-Protein Interactions: Using a combination of biophysical and biochemical methods, we aim to detail the molecular interactions between polyP and its protein targets, such as histidine and lysine repeats.
Investigating Functional Significance: By studying how PPM alters protein function, we hope to uncover new regulatory mechanisms, especially how these modifications affect protein activity and regulation.
Examining Cellular Implications: We are exploring the cellular consequences of PPM, focusing on its roles in stress response, signaling pathways, and possibly its involvement in disease mechanisms.

Beyond the study of PPM, our lab is also dedicated to researching atypical kinases, which have unique catalytic mechanisms differing from conventional kinases, and exploring their roles in cellular processes. Furthermore, we investigate host-pathogen interactions, particularly focusing on the development of antivirulence drugs as a strategy to combat bacterial infections by targeting virulence factors rather than bacterial survival, thereby reducing antibiotic resistance.

Our research combines a multidisciplinary approach, utilizing techniques in biochemistry, biophysics, computation biology, structural biology (notably X-ray crystallography), and cell biology. By combining these methods, we are advancing our understanding of polyphosphate's emerging roles in biological regulation and uncovering new therapeutic opportunities.

Please visit our lab website to find out more.

Selected Publications

N. Neville, K. Lehotsky and Z. Jia. (2024) Back on the chain gang: Polyphosphate modification of proteins. Trends Biochem. Sci. 49, 757-760.
N. Neville, K. Lehotsky, K.A. Klupt, M Downey and Z. Jia. (2024) Polyphosphate attachment to lysine repeats is a non-covalent protein modification. Mol Cell, 84, 1802-1810.
Z. Zhou, J. Jin, X. Deng and Z. Jia (2024) Protein purification via consecutive histidine-polyphosphate interaction. Protein Sci. 33:e5021.
N. Neville, K. Lehotsky, Z. Yang, K.A. Klupt, A. Denoncourt, M. Downey and Z. Jia. (2023) Modification of histidine repeat proteins by inorganic polyphosphate. Cell Rep. 42:113082.
N. Neville, N. Roberge, X. Ji, P. Stephen, L.J. Lu and Z. Jia. (2021) A dual-specificity inhibitor targets polyphosphate kinase 1 and 2 enzymes to attenuate virulence of Pseudomonas aeruginosa. mBio, 12:e00592-21.
W. Wu, Q. Shen, R. Zhang, Z. Qiu, Y. Wang, J. Zheng and Z. Jia. (2020) The structure of the MICU1-MICU2 complex unveils the regulation of the mitochondrial calcium uniporter. EMBO J. 39:e104285.
J. Zheng and Z. Jia. (2010) Structure of the bifunctional isocitrate dehydrogenase kinase/phosphatase. Nature, 465, 961-965.
D. Lee, J. Zheng, Y.-M. She and Z. Jia. (2008) Structure of Escherichia coli tyrosine kinase Etk reveals novel activation mechanism. EMBO J. 27, 1758-1766. (featured in Science)
Z. Jia, D. Barford, A.J. Flint and N.K. Tonks. (1995) Structural basis for phosphotyrosine peptide recognition by human protein phosphatase 1B. Science, 268, 1754-1758.
Z. Jia, M. Vandonselaar, J.W. Quail and L.T.J. Delbaere. (1993) Active-centre torsion-angle strain revealed in 1.6 Å resolution structure of the histidine-containing phosphocarrier protein. Nature, 361, 94-97.

Team

Faculty