Approved research

Infection dynamics: does genotype drive phenotype, and is infection more alike than unlike?

Lay summary

It is currently unclear why, although all of us suffer from infections from time to time, a small minority of us develop severe infections, or sepsis. Our current feeling is that sepsis is simply a result of 'bad' infection, from a particularly nasty bug, or a particularly unlucky person. This project aims to identify if people who get common infections have similarities genetically to those who develop severe infection requiring hospitalisation or even death. In particular, we also want to see the impact of different genetic makeup on whether people get different bugs, or whether people who have certain genetic types are more susceptible to many kinds of bugs. We would like to add to this information with measures of antibodies, proteins that we make to fight off bugs. Using all of this information, we would like to see if we can identify if sepsis is just 'bad' infection, or is more complex, by comparing people who have infections that don't require hospitalisation, to infections that lead to hospitalisation or even death. Finally, we know that we can already predict what kinds of people are likely to develop or die from infection using simple information, such as age, other medical conditions, smoking history etc. We want to know if adding genetic information can make that prediction better, and by how much. All of this would be useful information in helping us to explore and understand sepsis. Currently, we don't know why some people get sepsis, and although we know there is significant variety in the way patients with sepsis progress through their infection, we don't know if this is because of genetic differences, bug differences, or just plain luck. If we can understand the mechanisms that lead to severe infections, or infections with particular bugs, we can then start to explore mechanisms to prevent or treat these, in order to help treat people with sepsis better.