How Pathogens Interact with Human Cells
Our aim: To discover new ways of detecting, preventing and combatting human infectious diseases by discovering the mechanisms by which viruses and bacteria interact with human cells and tissues.
“We want to apply cutting edge imaging technologies to investigate the interactions of viruses and bacteria with human cells over time and with higher resolution than ever before. We hope that the knowledge we generate will lead to the development of new approaches for the treatment of infectious diseases.”
The ambition
That a better understanding how pathogens interact with human cells and tissues could pinpoint vulnerabilities providing new targets for antimicrobial therapeutics. A lot of current antiviral medicines disrupt how the virus replicates itself, but viruses can often overcome this. We think there is potential instead to find ways to block the virus entering the human cell itself as this mechanism is more conserved and less likely to be something the virus can escape.
What are we doing?
We will use innovative nanometre scale imaging techniques combined with data science, to visualise the dynamic interactions between a virus or bacterium and human cells, at the level of macromolecules, cells, and ultimately tissues.
Our platform technology for producing llama nanobodies, which are single domain antibodies, will help us identify, and track the specific proteins essential in host cell – pathogen interactions. Nanobodies are ten times smaller than antibodies so that, in combination with advanced imaging techniques, they can be used to pinpoint the location of targeted proteins very precisely. The application of novel chemistry within cells to modify protein function will give us even greater insights into the factors important in host-pathogen interactions.
Why?
As human disease-causing viruses and bacteria continue to evolve and evade current anti-microbial drugs and vaccines, there is a growing need for new treatments. A better understanding of how pathogenic viruses and bacteria interact with human cells and tissues could pinpoint vulnerabilities that provide targets for the development of new medicines.
Research examples
How RNA viruses hijack cells to cause infections
We will unpick the pathway that an RNA virus takes as it enters a human cell – from its first interaction with the cell surface, to how it moves into the cell and subverts the transcription and translation machinery of the host cell to replicate.
How intracellular bacteria establish persistent infections
We will investigate how a bacterium that can only survive by living inside human cells, evades host cell defences and hides in plain sight, leading to an ongoing infection.
Linked Franklin PhD projects
We are already investigating the structure and dynamics of Nipah virus: host cell interaction (collaborations with King’s College, London and University of Oxford).
Why the Rosalind Franklin Institute?
The Franklin is focused on developing the capabilities needed to image biological interactions across different scales, from molecules, to cells, to tissues and organs. Our researchers have interdisciplinary skills to navigate the physics, chemistry and biology necessary to make progress with this Challenge. We also provide a matrix team structure for research projects to allow us to be agile and cluster expertise around this Challenge.
