Science for Health
The theme of the 2006 Schools' Day was developmental biology, a subject that has fascinated biologists since they began to appreciate the variety of animal life and particularly the problem of how a fertilised egg becomes an organism with hundreds of different cell types, each with specific functions.
The afternoon began with presentations by scientists from the Institute who gave short talks about their work, based on the theme of developmental biology. Talks held included:
Dr Michael Sargent was funded by a Winston Churchill Travelling Fellowship to travel to Ethiopa, India and Canada. The purpose of his travels to these countries was to study a topic of great importance to developmental biology and with far-reaching significance for human welfare in the poorest countries of the world: the negative effects in later life of nutritional and other physiological stress on the developing fetus.
Dr Sargent's talk focussed on:
Dr Tiffany Heanue discussed the fascinating process in which cells from the central nervous system (the neural crest) undertake an epic migration into the developing gut and are transformed into nerves. Key players in guiding this process are protein growth factors and cell surface receptors.
A complicated network of nerves known as the enteric nervous system drives peristaltic movements of the gut. The cells that will form the enteric nervous system in a vertebrate embryo originate in a region of the central nervous system known as the neural crest. These undertake an epic migration from close to the head, along the developing gut, following a chemical trail formed by a chemo-attractant. Once in place, these cells begin to look like nerves and organise themselves into an electrical circuit that drives peristaltic movements.
The chemo-attractant is known to science because it is defective in a form of the genetic disease, known as Hirschsprung's disease. In infant victims of this disease with this, the enteric nerves fail to reach the end of the intestine. This means the developing gut cannot make the peristaltic movements essential for processing food and they survive only if the problem is corrected surgically. The chemical that attracts prospective nerve cells is a hormone-like protein called glial-derived neurotrophic factor (GDNF), which also plays an important part in forming the kidney. The migrating cells contain a receptor for GDNF that we presume organises their movement. The receptor was discovered through its involvement in a particular kind of cancer and consequently is known obscurely as RET. When the gut form of this receptor is defective, the victims have the same problem as babies with defective GDNF and require the same emergency surgery at birth.
Dr Charlotte Scott spoke about stem cells and the origin of new cell types. Differentiated cells such as neurones or blood cells are derived from cells with a capacity for unlimited cell division known as stem cells.
An important objective of developmental biology with immense practical implications is to discover the cues that can make these stem cells differentiate into histoligically recognisable cell types.
It takes about 46 cycles of cell division to make the ten trillion (1013) cells that constitute the adult human body and probably about 40 of those are done before we are born. Many cells of the adult human body cannot divide and our capacity to regenerate damaged tissues is quite limited. Unlike a newt, we cannot regenerate a missing limb! However our skin, blood cells, gut linings and livers can all regenerate by cell division.
The key to this process are stem cells which have an apparently unlimited capacity to divide, from which a proportion of daughter cells can develop into specialised (or differentiated cells). Cells of this type already have immense practical importance. Bone marrow transplants, for example, which contains stem cells for every blood cell type, can be used to permanently overcome a deficiency of any type of blood cell. Most kinds of stem cell make only a restricted range of differentiated cells. However, a fertilised egg is evidently quite different because every differentiated cell type of the human body is ultimately derived from this single cell type.
One of the most stimulating ideas to emerge from developmental biology is that cells from a very early mammalian embryo can be cultured indefinitely in the laboratory in an undifferentiated form (so called Embryonic Stem Cells). The really remarkable part is that conditions can be found where they can be made to differentiate into specialised cell types such as nerves or beating heart muscle cells. This is a very exciting idea because it suggests the possibility that these cells can be used to repair deficits caused by disease. Targets for such therapies include Parkinson’s disease and spinal cord injuries.
One of the key objectives of modern biological research is to understand at a sub-molecular level how proteins contribute to important processes. This involves a set of procedures that can give information valuable in resolving these problems. They were the subject of the presentation 'Understanding Proteins', by Dr Rob Orford.
Proteins are the most versatile family of biological chemicals in existence. They are chains of amino acids that can adopt an infinite variety of shapes with one of twenty alternatives at each position. They fold into precise structures, creating unique surfaces with a capacity to interact specifically with other chemicals and to catalyse chemical reactions. Proteins are the principle means by which living things create their structural and functional features.
To understand how proteins function is a key objective of biotechnology, so that the information can be used to solve medical and technological problems. Almost every protein has some intrinsic and special interest that can be studied by a set of general approaches.
Any protein can be made in large amounts in cellular factories using gene technology. This means that proteins whose existence is known only from a presumed protein coding sequence in the human genome sequence can be made in quantities that will allow physical, physiological and biochemical investigations. These proteins can be purified, crystallised and their structure determined in atomic detail using X-ray diffraction of the crystals and other techniques.
Knowledge of protein structure provides profound insights into all physiological functions. To the great enjoyment of the assembled throng, Dr Orford with the help of a visitor, showed how liver catalase can generate sufficient gas to inflate a rubber glove.
A break for refreshments provided the students with an opportunity to see demonstrations of some aspects of the development of mice, chicks, frogs, fish and flies. Posters relating to the theme of the meeting and showing work done by last year's Nuffield Bursary students were also on display. In addition, a poster exhibition of biomedical science news published in 2006 was used as a source for the quiz. Poster topics included:
The demonstrations were followed by a quiz, based on the day's presentations. A discussion panel concluded the day's events with scientists and graduate students from the Institute participating in a lively discussion that covered science, ethics and careers.
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