Our research program in molecular structural biology focuses on the elucidation of structure-function relationships of soluble and membrane-associated proteins and their complexes, with biomedical and biotechnological importance. We employ creative combinations of hybrid approaches involving X-ray crystallography, Small-angle X-ray Scattering (SAXS) and Electron Microscopy (EM), in conjunction with molecular interaction studies and cellular interrogation of the systems under study to elucidate the structural and mechanistic principles underlying the assembly, activation and pathophysiology of protein assemblies pivotal in inflammation, autoimmune diseases and cancer. The cornerstone of our research philosophy lies in a rigorous hypothesis-driven interrogation of the protein complexes under study, and is closely nested in collaborations with leading academic research groups in Belgium and abroad as well as industrial partners.
We are currently focusing on 3 main research topics:
- Pro-inflammatory signaling complexes.
- Extracellular assembly and activation principles of oncogenic receptor tyrosine kinases.
- Protein engineering and antagonist design.
In particular, our efforts to amass structural and mechanistic insights into the signaling assemblies under study are manifested via experimental work in the spirit of integrative structural biology to address the following:
- The architecture, interactions, and assembly principles of cytokine-receptor complexes
- The stoichiometry, affinity, thermodynamic profiles and kinetics for the association of the cytokines under study with their cognate receptors
- The plasticity and dynamics of cytokine and receptor modules
- The structural and evolutionary basis of receptor sharing, and its links to functional considerations
- The structural framework and mechanistic impact of somatic mutations identified in a number of the receptors under study
Structural basis of the proinflammatory signaling complex mediated by TSLPVerstraete K, Van Schie L, Vyncke L, Bloch Y, Tavernier J, Pauwels E, Peelman F, Savvides SNATURE STRUCTURAL & MOLECULAR BIOLOGY, 21, 375-82, 2014 Structural basis of IL-23 antagonism by an Alphabody protein scaffoldDesmet J, Verstraete K, Bloch Y, Lorent E, Wen Y, Devreese B, Vandenbroucke K, Loverix S, Hettmann T, Deroo S, Somers K, Henderikx P, Lasters I, Savvides SNature Communications, 5, 5237, 2014 Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1Elegheert J, Bracke N, Pouliot P, Gutsche I, Shkumatov A, Tarbouriech N, Verstraete K, Bekaert A, Burmeister W, Svergun D, Lambrecht B, Vergauwen B, Savvides SNATURE STRUCTURAL & MOLECULAR BIOLOGY, 19, 938-47, 2012
07/11/2016 - Researchers led by Savvas Savvides (VIB-UGent) gained surprising insights into how viruses use proteins to inactivate the immune systems of their hosts.
PhD: Cornell Univ., New York, USA, 2000
Postdoc: Washington Univ. School of Medicine, Washington, USA, 2000-02
EMBO Postdoc: Vrije Universiteit Brussel, Brussels, Belgium, 2002-04
Professor: Ghent Univ., Ghent, Belgium since 2005
VIB Group leader since 2015