Structural Biology of Infection and Immunity

Division of Structural Biology of Infection and Immunity

Dr. Erec Stebbins

Images of protein structures of bacterial virulence factors, the diffraction patterns from crystals used to obtain them, and the electron density (blue mesh) that serves as the data into which a chemical model is “built” for the molecule.
© dkfz.de

The goal of our research is to understand the molecular underpinnings of human disease, particularly those caused by microbial pathogens, and especially as they relate to human carcinogenesis. We use X-ray crystallography as a foundational tool for a "bottom-up" approach to these questions, examining pathogenic proteins and their interactions with host molecules at the molecular level.

Much of our work has to-date centered on bacterial pathogenesis, in particular bacteria utilizing specialized protein delivery systems, so-called "injectosomes" or "molecular syringes", machineries that translocate bacterial factors into eukaryotic cells to modulate host biochemistry for the benefit of the pathogen. Many of these factors are proven genotoxins or agents impacting oncogenic growth regulatory factors in the cell.

We also investigate the African trypanosome (Trypanosoma brucei), the causative agent of sleeping sickness. T. brucei repeatedly evades immune recognition through cycles of switching to different genetic variants of the extremely dense VSG surface protein, effectively changing its molecular appearance to the immune system through somatic, real-time "coat switching." We are using structural biology to examine the dynamic nature of this immune system-pathogen dynamic adaptational process. Our long-term goal is to develop paradigms for immune-evasion by pathogenic cell-types at the molecular level, which we hope will inform studies of immune-evasion in other contexts such as cancer.

Contact

Dr. Erec Stebbins
Structural Biology of Infection and Immunity (D160)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42-1380

Selected Publications

  • D. Nesic, L. Buti, X. Lu, and C.E. Stebbins. (2014) “Structure of the Helicobacter pylori CagA Oncogene Bound to the Human Tumor Suppressor Apoptosis-stimulating Protein of p53-2 (ASPP2).” Proc Natl Acad Sci Jan 28;111(4):1562-7
  • R.Q. Notti, S. Bhattacharya, M. Lilic, and C.E. Stebbins. (2015). “A common assembly module in injectisome and flagellar type III secretion sorting platforms.” Nat. Commun. May 21;6:7125 doi: 10.1038/ncomms8125. PMID: 25994170
  • J. Pinger, D. Nešic, L. Ali, F. Aresta-Branco, M. Lilic, S. Chowdhury, H-S. Kim, J. Verdi, J. Raper, M.A.J. Ferguson, F. N. Papavasiliou, C.E. Stebbins. Nature Microbiol. (2018). “African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat." Nat Microbiol. Aug;3(8):932-938. doi: 10.1038/s41564-018-0187-6. Epub 2018 Jul 9. PMID: 29988048
  • F. Aresta-Branco, E. Erben, F.N. Papavasiliou, C.E. Stebbins. (2019) "Mechanistic Similarities between Antigenic Variation and Antibody Diversification during Trypanosoma brucei Infection." Trends Parasitol. 2019 Apr;35(4):302-315. doi: 10.1016/j.pt.2019.01.011. Epub 2019 Feb 28. PMID: 30826207
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