The ecosystem within us and the silent serpents

We are all familiar with the adverts in the media encouraging us to keep our digestive tracts healthy by eating probiotics such as yoghurt drinks – to promote the “good bacteria” in our gut. Our gastrointestinal tract contains billions of bacteria made up of populations of many different species, ideally living as a balanced community – and can be considered as our own internal ecosystem. The strains and stresses of modern living are thought to upset this ecosystem – hence the use of “good bacteria” to re-set the balance.

The intestine is also a major site of potential infection by many organisms. It is becoming clear that such infections may upset our intestinal ecosystem too, often by upsetting the normal functioning of our bodies’ immune system.

Research teams in microbiology and immunology here in Manchester have identified another important player in the intestinal ecosystem – parasitic roundworms. These are some of the most common infections of man and animals worldwide with over two billion people currently infected mostly in the developing world, although until relatively recent times everyone would probably been infected. These parasites evolved to live within us throughout the ages and would have been in our intestines for most of our lives. Researchers in Manchester have now shown that intestinal roundworms have a profound influence on the bacteria found in the intestine. Moreover, the parasites exhibit a highly evolved relationship with the gut bacteria in which the intestinal microbes actually help the parasite eggs to hatch in the intestine. Finally, the immune system is influenced by the bacteria to alter immune response to the parasites allowing them to survive in balance with the bacteria. Identifying how the bacteria, worms and immune system work together in concert may generate new ideas of what constitutes a healthy balanced intestine.

Read more about related research:

Immunology and Molecular Microbiology Research Group
Manchester Immunology Group

Could you love a chemical baby?

The scientific use of human tissue and cells has become controversial. To many people it typifies a longstanding divide between science and the public. Critics claim that scientists view tissue and cells as a scientific resource and have long worked in secret. They suggest that public resistance to such developments is because scientists ignore public demands for openness.

One technique that often features in such discussions is tissue culture, which involves the maintenance of human and animal material in laboratory conditions. Duncan Wilson’s new book, Tissue Culture in Science and Society (Palgrave, 2011), sheds new light on tissue culture’s history. He shows that, from its first development in 1907, as well as being discussed at scientific meeting and in journals, it also appeared in films, newspaper reports and fictional stories.

The book challenges claims that popular attitudes to research on tissues are always negative, unchanged and opposed to science. It shows how popular interest changed over time, in line with broader concerns: from interest in ‘better breeding’ during the 1920s, to the development of new therapies during the 1950s, and patient rights from the 1980s.

Dr Wilson demonstrates that there was two-way traffic between scientific and popular concerns. Far from operating against public attitudes, scientists who used tissue culture drew upon and influenced them. For example, in 1926 Thomas Strangeways drew on interest in ‘better breeding’ to claim that tissue culture legitimated ‘the test tube baby’. This was widely reported by newspapers and informed novels like Brave New World; and these popular sources, in turn, influenced the ways that scientists presented and used tissue cultures.

Read more about related research on the CHSTM website.

Wriggling towards new therapies

‘The smallest worm will turn’ (Shakespeare Henry VI Pt 3) and it is the precise and automated measurement of the left and right turns of a swimming nematode worm that is helping David Sattelle, Manchester University’s Professor of Molecular Neurobiology, in the search for a new drug to help patients suffering from a devastating neuromuscular disorder.

Spinal muscular atrophy (SMA) is one of the principal genetic causes of infant mortality. It has no effective treatment and in SMA patients certain motor neurons degenerate leading to muscle wasting, which in the most severe cases results in paralysis and death.

The researchers therefore ‘turned’ to the worm (C. elegans) which has perhaps the simplest nervous system on the planet (302 neurons) but nevertheless includes well-mapped, motor neurons. It was the first animal to have its entire DNA (genome) sequenced. A change in a single letter of the DNA code, at the equivalent position to such a change in the DNA of a patient suffering from spinal muscular atrophy, slowed down the frequency of the left-right turns.

David and his Oxford colleagues, James Sleigh and Dr Steven Buckingham, developed new instrumentation and software to rapidly analyse ‘worm turning’ and harness it for testing whole libraries of drugs, including some, with possible utility for SMA patients, which have successfully negotiated safety approvals for other diseases, as well as exploring novel chemistries for their ability to rescue or ‘treat’ the turning defect. The initial encouraging results were obtained while David was working in Oxford University’s Medical Research Council (MRC) funded Functional Genomics Unit and he is first to acknowledge his indebtedness to the MRC. Following his recent move to Manchester his laboratory has been awarded a grant from SMA Europe to extend the search for treatment to even bigger chemical libraries.

Human Mol Genet 2011 paper

Read more about related research in the Neurosciences research group.