During an infection, pathogens circumvent the host’s immune defenses via the expression of highly evolved virulence factors which hijack and re-wire the host’s molecular systems. At the same time, host proteins and cells of the innate and adaptive immune system bind to bacterial surfaces and virulence factors to neutralize the invading pathogens and prevent infection. An in-depth understanding of these molecular level events is not only essential for the understanding of disease on-set, progression, and host-immune evasion but also for the discovery of new targets for therapeutic intervention, and for the development of biotechnological applications.
Two tools have revolutionized structure-based discovery of novel proteins, AlphaFold and Foldseek. AlphaFold does very accurate predictions of 3D structures using AI, whereas Foldseek can be used to identify predicted or determined structural homologues with very low amino acid sequence identity. We have used AlphaFold and Foldseek to identify putative and novel virulence factors expressed by different human pathogens and are now looking for a motivated MSc student (45 of 60 hp) to characterize one of these.
The project is centered around the characterization of the host interactomes of these virulence factors by quantitative affinity-purification mass spectrometry (MS) and structural proteomics (cross-linking and hydrogen-deuterium exchange (MS)). We are also interested in discovering whether the virulence factors contribute to further virulence mechanisms, such as host DNA degradation, which is a common trait to several of the enzymes we are currently studying. In addition to MS, the project will include methods in basic biochemistry, such as SDS-PAGE and western blot analysis, ELISA-based assays, nuclease activity assays etc…
We are looking for a student with experience in functional protein characterization and some of the biochemical methods listed above. No previous experience in MS or MS data analysis is required.
Our research group in Structural Infection Medicine is located at the Division of Infection Medicine at BMC in Lund. The group consists of a PhD student, who will be the co-supervisor of this MSc thesis and MSc students. The research group is working closely together with five other research groups, comprising of clinicians, preclinical researchers, PhD students, research engineers and technical laboratory personnel.
For more information, please contact the group leader Lotta Happonen, lotta.happonen@med.lu.se.