Research Opportunities

Understanding HIV incidence at a population level is critical for monitoring the epidemic and understanding the impact of interventions. Using full length sequencing of HIV we are developing models for estimating incidence based on viral diversity which increases with time in the infected host. Using data from longitudinal cohorts we will develop these models and then apply them to large population based interventions to determine their impact.  Experimental approaches include next-generation sequencing, phylogenetic analysis, modelling and statistical methodologies.

The last decade has witnessed repeated emergence of RNA viruses with high pathogenic potential in humans including SARS-CoV-2, Zika virus, yellow fever virus and Ebola virus. The inflammatory response to infection is a major driver of pathogenesis, but the molecular mechanisms by which these viruses initiate and dysregulate inflammation are not well defined. Mitochondria are now recognized as critical regulators of the immune system and inflammation, serving as both signaling platforms and as sources of danger-associated molecular patterns (DAMPs) to initiate diverse signaling pathways. SARS-CoV-2, like other positive stranded RNA viruses, uses membranes derived from the ER for their replication factories, but also actively manipulates mitochondria, Golgi apparatus and other membrane bound organelles for replication purposes. However, it is unclear why mitochondria are hijacked during viral replication, and what the consequences of this manipulation are to inter-organelle communication and inflammation. This PhD project will use SARS-CoV-2 infection models in tissue culture and mouse models coupled to cutting-edge microscopy analysis to determine novel ways in which mitochondrial membrane remodelling and organelle contact sites are controlled, and the importance of these events as drivers of inflammation.

A previous infection with one of the four dengue viruses increases future risk of severe dengue disease, including hemorrhagic fever, upon infection with a different dengue virus. For this reason, dengue viruses 1-4 are challenging vaccine targets because sub-protective vaccines can increase risk the disease vaccines are designed to prevent. In the Viral Epidemiology and Immunity Unit (Chief, Dr. Katzelnick), we aim to identify correlates of natural and vaccine protection and antibody-dependent enhancement in order to develop better next generation vaccines, extend the longevity of vaccine-induced immunity, and characterize how vaccines may affect viral evolution and transmission.  Our work combines immunology, virology, and epidemiology, including close collaborations with research teams leading longitudinal cohort and vaccine studies in Nicaragua, Sri Lanka, Thailand, Ecuador, the Philippines, and other sites. Specific projects include studying quaternary ‘super-antibodies', which bind epitopes across viral envelope proteins, and testing whether these antibodies provide enduring protection against dengue and other viral diseases. We will also study antigenic evolution away from existing immunity for flaviviruses and coronaviruses. Dr. Katzelnick was part of the NIH OxCam program (2012-2016) and is open to collaborating with research groups at both Oxford and Cambridge to mentor Ph.D. students.