Mouse airway epithelial cultures

2012 Teachers’ Day

In 2012 we once again 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. This year we addressed three ideas with a special place in modern biomedical thinking: the significance of protein growth factors in shaping cell fate; the importance of structural studies of proteins; and how we conceptualise the processes by which the nervous system performs its miraculous functions.

Abstracts

What drives formation of the nervous system of the gut?

Tiffany Heanue

The complicated network of nerves that drive the peristaltic movements of the gut have a complicated and interesting origin quite distinct from the embryological origins of the gut itself. These nerve cells originate from undifferentiated cells that separate from the central nervous system in a region close to the head. These start an epic migration along the developing gut, following a chemical trail formed by a hormone-like protein secreted by gut tissue called Glial-derived Neurotrophic factor (GDNF) (which also has an important role in forming the kidney). Once in place, these cells take on a neuron-like appearance and organise into an electrical circuit that can drive peristaltic movements. The migrating cells contain a receptor for GDNF known as RET (discovered initially because of its involvement in certain cancers) that organises the movement of these cells. Its importance is revealed in babies born with a moderately rare genetic disease (one in 5,000 births) known as Hirschsprung's disease, in which the enteric nerves fail to develop to the end of the intestine. The babies survive only if the problem is corrected surgically because otherwise they cannot make the peristaltic movements essential for processing food in the gut.

Physical methods help us understand how proteins engineer programmed cell death and other biological activities

TJ Ragan

About 1% of all cells in the human body disappear every day, leaving no trace of their existence. This is engineered by a process known as apoptosis, or programmed cell death, in which cells are destroyed at astonishing speed and the debris is dispersed so discreetly that the immune system is not alerted. Apoptosis came to the attention of a wide audience when genetic studies with the tiny nematode worm Caenorhabditis elegans revealed that cell-death was programmed to occur at precise times and places. Apoptosis is also important in other organisms, and was the subject of the 2002 Nobel Prize for Medicine. It seems that any cell in the body might die by apoptosis if it is not sustained by an appropriate growth factor. This provides a level of control over cells that integrates their functions. B or T lymphocytes that were activated during an infection are normally eliminated from the body by programmed cell death. Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare genetic disease in which programmed cell death fails to eliminate the unwanted lymphocytes. This causes chronic non-malignant proliferation of the lymphocytes leading to autoimmune disease. We study this process by nuclear magnetic resonance (NMR) spectroscopy to determine the three dimensional structure and dynamic properties of these molecules.

Facebook; a metaphor for the mammalian nervous system

Ede Rancz

Neurons, the most remarkable cells in the human body, form the hugely complex circuitry of the nervous system. Our brains contain perhaps 100 billion neurons and they have more connections between them than there are stars in our galaxy (>100 trillion connections). Neurons orchestrate our behaviour, movement, awareness of the environment and the profound functions that permit communication or expression of personality traits. The neuron-to-neuron transfer of electrical impulses through synapses can be strengthened or weakened by the process of ‘plasticity’ that is thought to be the physical basis of forming memories and generating ideas. Neurons work together in neural networks but with different networks for different functions in arrangements that seem almost too complex to imagine. Dr Rancz showed how this can be understood in principle using Facebook as a metaphor. The long term aim of neurobiological research at NIMR focuses on understanding how sensory information is processed to produce perception, behaviour and decision-making.

 

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