Professor Derrick Crook's research consortium focusses on translating new molecular technologies and advances in informatics into the investigation of microbial transmission, diagnosis of infectious disease and identifying outbreaks of communicable disease. This research aims to translate deep sequencing of pathogens on an epidemiological scale for tracking infections, and is focussed on four different major pathogens: Staphylococcus aureus (including MRSA), Clostridium difficile, Norovirus and Mycobacterium tuberculosis.
Understanding how an infection spreads is vitally important for prevention. Whole genome sequencing of microorganisms allows us to construct family trees of infections, from donnor to recipients, and understand how microbes behave in general. Through its genetic code, we can also predict whether a germ is susceptible or resistant to a specific antibiotic, and give patients a more stratified and personalised treatment.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Q: Why do we need to track infections?
Derrick Crook: One of the characteristics of infection is it spreads either between people, or from the environment, or from other animals. And knowing how it spreads is vitally important to being able to devise methods to interrupt that spread and therefore prevent infection.
Q: How can we use molecular technologies to track infections?
DC: That has really been strengthened through the technology developments, particularly those that have to do with generating the whole genome sequence, which is the whole code, like a barcode of the microorganism. That information can be used to construct the most detailed, very fine scale family trees. From the family tree you can look where the progeny has come from. The progeny of the product, or of the transmission change, from there you can de-convolute, you can find a way of expressing exactly how microorganisms are spreading remarkably accurately.
Q: Can you give us an example of when an infection was successfully tracked?
DC: There are a number of circumstances where this sort of tracking has been well done, but one stands out in particular which is TB (tuberculosis). This is an organism that infects man and spreads from person to person principally. It is vital to understand who gave it to whom, and indeed one person can give it to many other people. We have really elegant examples of work that we've done ourselves, and work that colleagues have done both in the UK and abroad. We were able to identify a network of transmission and understand it very precisely, and indeed have identified ex post facto the donors. So you find the recipients, the people that got the infection, and you are able to pin point the person who was the donor. Interestingly enough, some of these family trees show that a donor is missing, and you are able to go and find the donor. This is a remarkable way of taking network information, looking at it and understanding where parts of it are missing, and then through clever "shoe-leather epidemiology", going and talk to people and asking questions, identify the missing source.
Q: What are the most important lines of research that have developed in the last 5-10 years?
DC: The research we are doing now has benefited from a technology development which means that you can get the whole genetic code through sequencing, and that enables you to have an extraordinarily detailed map of that code. Comparing the maps of that code, you are able to identify these transmission chains that have practical use, but they also give us fundamental understanding about how microbes behave in general. This has been a revolutionary advance in the whole field of infectious disease.
Q: Why does your research matter and why should we fund it?
DC: I like to think of that as something easy to answer. There are two ways of looking at it; on one hand we are getting a fundamental understanding of how germs spread. That can be used in practical ways: you are able to do investigations that give you a detailed understanding of microorganisms, and you can then translate that into medical practice. On the other hand when you get the genetic code you do not only use it to understand how an organism transmits, there is also a huge volume of data, and you can mine that code for other things. The most useful thing for treating people is that in that code you can tell whether the germ is susceptible to antibiotics or resistant. By knowing it is resistant you can avoid using drugs that are not going to be effective, or if you know it is susceptible you can use drugs that will work. This genome sequencing is becoming so rapid now that you are likely to be able to take a sample and within the same day, even in a few hours, provide the information that enables you to give a very personalised or stratified treatment, tailored to the particular problem to hand.
Q: How does your research fit into translational medicine within the department?DC: Along with other activities that have to do with taking genome sequencing and purposefully putting it to medical diagnostic use to better treat patients, it fits perfectly in that applied translational sense in the activities of the department.