Dr Julian Knight studies how genetic variation between individuals affect the way immune and inflammatory genes are expressed. This helps understand genetic susceptibility to common conditions such as infectious, inflammatory or autoimmune diseases. He recently published a book titled ‘Human Genetic Diversity, functional consequences for health and disease’.
Genetic variation plays an important role in individual susceptibility to many common diseases. New insights into genetic variants which modulate gene expression allow us to better understand why people develop these diseases. We can then target treatments much more effectively. Ultimately, we will be able to identify patients at risk of developing disease.
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: Julian, how much can we blame our genes when we fall ill?
JK: That really depends on the disease that we're talking about. There are some diseases which are relatively rare and run very clearly in families, such as cystic fibrosis or Huntington's disease, where there are particular genes and mutations in those genes that have a very major effect and are responsible for the disease. There are other diseases which are much more common, such as diabetes or asthma, where the effects of individual genetic variants are relatively small but cumulatively when we think about the many different genes that can be involved they can have quite a large effect.
Q: What are our current tools to map genes with disease susceptibility?
JK: Well we live in really exciting times in genetics at the moment and there have been some very rapid technological advances that have meant that over the last 10-15 years we now have the sequence of the human genome. We are now able to identify genetic changes between different patients and we can do this for hundreds and thousands of different genetic variants in a given patient. This has meant that over the last few years it's been possible to begin to understand the genetic basis of common disease by studying thousands of patients with a particular disease and comparing the genetic variation in those patients with controls. That's highlighted how we now realize that many genes can be involved in a particular disease and genetic variants of those genes.
Q: You are interested in genetic variation of genes involved in immunity and information. How can this help patients?
JK: I think that immunity and information are really at the heart of many different diseases. What we try and do in our research is to understand how the normal response in terms of immunity and inflammation can vary between people and in particular in specific disease context because if we can understand that variation then we can perhaps try and use the treatments that we have available now more effectively so that we maximize benefit for the patient and minimize the risk of adverse effects and also get new insights into why disease develops because through genetic studies we're finding completely unexpected processes that are underlining disease that we weren't aware of before we had these new genetic tools.
Q: So why did you write your book?
JK: Well these are very fast moving times in genetics and I wrote the book really for undergraduate and graduate students to provide some historical context in terms of current human genetic research to identify some of the landmark discoveries that have got us where we are now and also to provide a broader view if you like of the many different types of genetic variations that we now realize exist and also how this is impacting in many different areas of research ranging from clinical medicine through to evolutionary biology. And hopefully through this book I can bring some of the enthusiasm that we have for genetics at the moment and inspire others to continue in this area.
Q: Why does your line of research matter? Why should we put money into it?
JK: Well I think that a lot of money has gone into genetic research over the last 10 to 20 years and that is starting to bear fruit. Our understanding of the nature of genes and how that varies between people is becoming much clearer and it's providing new insights into why people develop disease and also allowing us to target treatments much more effectively. I think that over the next 5 to 10 years we will be seeing rapid advances in how we use genetic information to try and personalize patient care for the individual so that they can get the maximum benefit from treatment that's available and also perhaps allow for better screening and identification of patients at risk of developing disease.
Q: So finally I guess that's how you feel your research fits into Translational medicine within the department?
JK: There is a need for us to try and translate the advances that have been made in genetics into differences in patient care. The work that we do I think complements a lot of other groups within the department who are taking mainly population genetic approaches to try and identify genetic variants that are important in particular diseases. Our work, if you like, takes a more functional approach to identify at a mechanistic level how particular genetic variants might be important in modulating gene expression and in turn the risk of disease. So this helps us narrow down on particular genetic variants and identify those variants that are most important and which could be of use to doctors in the future in terms of predicting risk and also tailoring treatments most effectively to the individual patient.