Strains of M. tuberculosis during infection

2011 Teachers’ Day

In 2011 for the second time we invited teachers from local schools to our Teachers' Professional Development Day. The idea was to present talks on recent research at NIMR that would add to subjects which are part of the A level curriculum or which are of general interest. There were two lectures spanning developmental biology and genetics, and another two on immunological subjects.

Abstracts

Meiosis: The crucial stage in chromosomal physiology that makes genetic re-assortment possible

James Turner

Meiosis is the crucial stage in chromosomal physiology that makes evolution and genetic diversity possible. While it has had a prominent place in the school curriculum for many years, it is a subject that still poses important and interesting questions for researchers that can be answered with new technologies. Examples include: How does the cell orchestrate the gymnastics required to separate homologous chromosomes? Why does this process become less effective in older females so that the risk of non-disjunction becomes severe in their 40s? and why is it less of a problem in males? How are sex chromosomes separated when they do not form homologous pairs?

How vertebrates make their limbs; new methods of studying gene function

Malcolm Logan

Limbs emerge in vertebrate development in exactly the right place at a very early stage. Initially, forelimbs and hindlimbs look identical but quickly take on their definitive differentiated form. The role of specific genes in this process can be studied very effectively in several types of vertebrate embryos both by interfering with specific functions and showing where crucial molecules are expressed. The tissue elements in limbs (e.g. bones, muscles etc) have complex anatomical arrangements but a clear hierarchy of genetic controls is apparent and we now largely understand the processes that determine whether a limb bud will develop into a fore or hindlimb.

With our knowledge of the master-genes that initiate limb development it was interesting to reflect on where in the tree of life they first appeared; we can report that homologues of these genes are present in Amphioxus, a limbless protochordate. This research is also relevant to the substantial number of human genetic diseases that affect limb development and the response of embryos to teratogenic chemicals (eg thalidomide).

The origins of allergy and autoimmunity

Mark Wilson

The human immune system has a remarkable capacity to deal effectively with billions of foreign antigens and yet tolerates the distinctive collection of potential antigens in our own tissues (self) in our own bodies. For a significant number of people, this tolerance breaks down, leading to the development of autoimmune and allergic diseases. The hygiene hypothesis attributes this breakdown of tolerance to a lack of childhood exposure to microbes that limits development of the immune system and specifically that anti-viral, bacterial and parasitic immune responses could prevent the development of autoimmune and allergic reactions.

While this may still be true, it now appears that the response to infectious pathogens must be balanced and regulated to prevent allergies and autoimmunity. A third dimension to the hygiene hypothesis is the part played by chronic pathogens when they are able to subvert our immune system. Evidence that pathogens, particularly chronic pathogens directly interfere with our immune system is now very clear. Mark Wilson will describe the approach he uses to study the causes of allergic airway disorders and autoimmune reactions in mice.

New ways of studying Tuberculosis

Anne O’Garra

Tuberculosis is a disease caused by the microbe Mycobacterium tuberculosis that still kills approximately 1.7 million people per year. A third of the world population is probably infected with M.tuberculosis but is asymptomatic. These infections, which are described as 'Latent', have a 10% chance of developing into active tuberculosis (TB) and therefore present significant risks to public health as the individuals at risk are not easily identified. The immune response to M.tuberculosis has been studied for more than a century but there is clearly much to be learned.

Anne O’Garra has undertaken a far-reaching investigation of humans infected with M.tuberculosis, to identify the mRNA molecules made by blood cells in response to infection. Many of these mRNAs would be produced in response to other infectious diseases or inflammatory episodes but a set of them appear to be specific to active TB disease. This mRNA 'signature' correlated with the extent of the disease in the lung revealed by X-Ray and disappeared when the patients were treated successfully with drugs. A subset of the individuals with Latent TB produce a set of mRNAs found in active TB, suggesting these individuals are at substantial risk of developing the disease. The response observed in TB was dominated by mRNAs induced by interferons —anti-viral proteins secreted from cells called neutrophils. This included Type I Interferon induced genes which may exacerbate TB. This investigation has provided a broad range of biomarkers with potential for diagnosis of latent infections and has implications for the development of vaccines and therapy.

 

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