Case study: Tackling inflammatory bowel disease
Although there are drugs available to treat inflammatory bowel diseases, patients often relapse, which makes it even harder to tackle the disease in that patient in the future. Precisely why some patients relapse and don’t respond to existing drugs is the focus of a long-term study by researchers in the Immunology group at the University.
There are two main forms of Inflammatory Bowel Disease (IBD): Crohn’s Disease and Ulcerative Colitis. Crohn’s is a condition that can cause inflammation along the entire length of the intestine, while Ulcerative Colitis causes inflammation and ulceration of the inner lining of the rectum and colon.
Researchers are trying to identify how cells of the immune system are controlled in the intestine to prevent IBD. In so doing, the team can identify molecules that it can then target for therapy.
As Dr Mark Travis explains: "We are trying to understand the basic pathways, to understand what is going wrong, and why. The immune system has evolved to protect the body from harmful pathogens, and to function properly it must be tightly regulated so that it is switched on and off only at appropriate times and in appropriate locations in the body. It is when this regulation is compromised that disease situations can arise."
The study of immunology is evolving fast, thanks to the discovery of many new types of cells involved in regulating immune responses.
As Dr Travis adds: "At the most basic level, humans have a gene which makes a specific protein. If you are able to block the function of this protein with a drug, that in turn gets rid of a particular pathway in the body.
"We can model this in mice, by removing that gene, which can tell us a great deal about what that specific gene and protein are doing. Ultimately, the only way of solving diseases is by fully understanding how the system works in the first place.
Ultimately, the only way of solving diseases is by fully understanding how the system works in the first place.Dr Mark Travis / Principle Investigator
"The analogy I use is a car and a mechanic. Biology is like a system: you are working out how everything works. There is always more to discover and the complexity means you never fully understand everything. Finding something new also means you then have to reinterpret all the research you have looked at before in the light of the new findings."
A specific focus of study is on a protein known as the TGF-beta, a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation and cell differentiation.
Adds Dr Travis: "This is a key molecule involved in regulating the immune system and is secreted from cells in an inactive form that needs to be activated to exert effects on cells. We have recently identified the integrin receptor, alphavbeta8, as an important activator of TGF-beta in the immune system. Disruption of this pathway in specific immune cells results in a loss of immune homeostasis, resulting in self-harmful immune responses."
Dr Travis says that only by studying the immune system of animals such as mice can you begin to answer these complex questions.
"Animals provide important mechanisms to test directly how cells and proteins are involved in a range of immune responses. In particular, the mouse immune system is a very good model for humans and many of the key discoveries relating to immune cells and processes have been found first in mice.
"Because there has been so much research into mice, we have built up a legacy of information about their cell make-up. Technology now allows us to specifically knock out genes from specific cell types in the mouse, to get detailed information on how the immune system communicates to promote health, and how this breaks down during inflammatory disease."