General research interests

A) The intestine is a continuous tube from mouth to anus, and the bacteria live inside this tube, but because the lining of the intestine is extremely thin - a layer just one cell thick - small numbers of commensal bacteria and their molecules are continuously penetrating the body tissues. The cells and antibodies that make up the body's defences against foreign microbes are called the immune system, and a major part of this system is in the lining of the intestine. We know that the mucosal immune system is important for protection against commensal intestinal bacteria, because we can follow its development as germ-free animals without any intestinal microbes are colonised with commensal bacteria. Unfortunately, antibiotics reduce but do not eliminate intestinal microbes, so there has been no way back to a germ-free condition once bacteria have populated the intestine. We have engineered new bacterial strains that cannot survive long in the intestine, so colonised mice become germ-free again. We are using this system to measure the threshold for inducing an IgA antibody response against commensals, and whether the immune system in the gut 'remembers' previous encounters with commensal bacteria and generates a stronger response on the second occasion (as in medical vaccinations). We are also working out how effective this immune response is, on its own, to protect the tissues of a germ-free animal from bacterial penetration, without competition from resident intestinal bacteria

Research Interests

B) Healthy humans and other animals have enormous numbers of bacteria and other microorganisms in the lower intestine. These are very good for us as they help us harvest energy from food, provide us with vitamins, break down toxic chemicals and prevent pathogenic bacteria from causing disease. For health, these commensal microbes must be contained inside the intestinal tube, but allowed to flourish. In this project we will study the way in which the main antibody of the body, IgA, is secreted into the intestine to promote the peaceful coexistence of intestinal commensal bacteria and the host. We will focus on how live microbes are prevented from entering the tissues of the body, yet provided with the right environment next to the intestinal membrane to form stable growing communities.
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