Investigating the cell’s defences when under viral attack

Investigating the cell’s defences when under viral attack

Dr Ben Ravenhill, an Internal Medicine Trainee and Academic Clinical Fellow at Addenbrooke’s was recently awarded funds by the Evelyn Trust to investigate how cells defend themselves when under attack from a flavivirus.
Ben Ravenhill at work in the lab

Ben Ravenhill at work in the lab

Flaviviruses are viruses commonly transmitted by mosquitos and up to 40% of the world’s population is at risk of these serious infections, including Zika and Dengue. Zika hit the headlines in recent years when it became clear that the babies of pregnant women who were infected were at risk of microcephaly and other serious brain defects.

Dr Ben Ravenhill, an Internal Medicine Trainee and Academic Clinical Fellow at Addenbrooke’s was recently awarded funds by the Evelyn Trust to investigate how cells defend themselves when under attack from a flavivirus. When a cell detects invasion by a virus, it fights against the invader by making antiviral proteins. Ben’s plan was to look at the changing levels of proteins in cells after infection, aiming to identify new candidate antiviral proteins that are made by the cell and then degraded by the virus. With more knowledge of antiviral defences, the ultimate long term objective would be new antiviral medications.

With flaviviruses so high on the research agenda worldwide, Ben found, at an early stage of the project, that another research team had sought to answer the same questions and published their results. 

“I’ve been really grateful to the Evelyn Trust for allowing me to change my research objective and continue with my work on cell defences. I’ve adjusted the project to investigate the mechanisms within cells that sense when the virus has invaded. I am looking at virus sensing pathways, which would detect viruses such as Dengue, etc, but using cells infected with Sendai virus which provokes a strong immune response.

“We have infected large numbers of cells and then split them into their component parts: nucleus, cytosol and organelles. We already know that proteins involved in sensing viral infection can move within the cell once a virus is detected. I had questions about whether we could identify any undiscovered antiviral proteins that move within the cell. I now have some very strong data of new proteins which do indeed move from the cytosol to the nucleus in response to infection and we’ve also identified a list of proteins that move in the other direction. The reasons why they move are not yet entirely clear, but I believe it’s likely that the proteins move in order to alter the ‘on’ state of some genes – switching them on as part of the cell’s antiviral response,” explains Ben.

Ben’s one year research project has now come to an end, but as a researcher with Dr Mike Weeke’s Lab at the Cambridge Institute of Medical Research, his important work on the cellular basis of infectious diseases will continue.

There’s more detail on the fascinating work of the Cambridge Institute of Medical Research at www.cimr.cam.ac.uk

 

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