MRC National Institute for Medical Research, London
Science for Health
Schools’ Day 2004
The theme of the 2004 meeting was individuality of tissues.
Talks
The afternoon commenced with younger scientists from the Institute who gave twenty-minute talks about their work, based on the individuality of tissues:
Blood - a fluid in blood vessels that clots in wounds - Dr Tom Carter
Many decades of research indicate the physical state of blood in the human body is controlled with extraordinary delicacy. If a clot forms in a blood vessel it may cause a catastrophic shortage of oxygen in critical tissues and yet clotting is an essential rapid response to accidental injury to prevent leaks that could be life-threatening or a route for infection. Understanding how these processes are controlled is a vital aspect of medical research because unregulated clot formation in middle age is responsible for heart attacks and strokes. Individuals with thrombophilia are genetically predisposed to make blood clots easily, a condition that can lead to deep vein thromboses.
The role of the endothelial cells that line blood vessels in controlling blood clotting was a key part of Tom's talk. These cells secrete proteins, such as von Willebrand's factor (vWF) and Factor VIII, that are important for blood clotting and others that antagonise the process, regulate blood flow and mediate local inflammatory responses. The proteins are packed into membrane-enclosed particles for secretion; vWF in large specialised granules called Weibel-Palade bodies and the anti-coagulation proteins in distinct small particles. A video made using a fluorescent derivative of vWF gave a vivid image of the secretion process.
Creating the brain - how cells recognise their neighbours - Dr Marisa Cotina
The most highly organised tissue in the human body, the brain, is profoundly mysterious to biologists because although it contains billions of a few cell types (neurones and glia), they are intensely specialised at a local level. To start understanding this we need to know how such extraordinary organisation emerges during the development of vertebrate embryos. Marisa Cotina discussed experimental approaches, pioneered at NIMR, for studying the early steps leading to formation of the hindbrain of the zebrafish.
The tissue that will become the vertebrate hindbrain is first subdivided into segments, known as rhombomeres from which nerves migrate to form characteristic links with particular parts of the body. Cells in neighbouring rhombomeres do not mix so that adjacent rhombomeres develop in different ways, expressing different and characteristic genes. A pair of proteins appears on the surfaces of cells within the hindbrain; one on rhombomeres three and five, the other on rhombomeres two and four. If these proteins make contact with each other, they promote repulsion between cells and between neighbouring rhombomeres. The two kinds of protein almost certainly have a more general role in ensuring neurones make contact with the right organs during the development of the embryo.
Muscle - how actin and myosin generate force - Dr Stephan Schmitz
The third kind of tissue considered was muscle. Stephan explained the deep insights that physical biochemists bring to understanding the way these extraordinary assemblies of specialised cells use the proteins myosin and actin to transform energy from a chemical to a mechanical form and make muscle contraction possible. The ability of actin and myosin to move relative to each other was predicted many years ago. In a compelling video-demonstration students were shown how actin molecules, labelled with a fluorescent dye, move across a layer of myosin when provided with ATP as a source of chemical energy. All three components are pure chemicals, so no further element is required to explain the observed movements. Underlying this phenomenon is a process in which the cross-bridge between myosin and actin moves like a ratchet, to a new position on the actin molecule with the release of chemical energy from ATP. The individual tiny movements of one pair of molecules is multiplied by a very large factor in an entire muscle.
Stefan also illustrated the power of physical biochemistry in studying muscle contraction using another technique called 'molecular tweezers' to measure the force and movement produced when a single myosin cross-bridge is formed. By studying different kinds of myosin and actin, scientists at NIMR and elsewhere are acquiring a deep knowledge of the chemical properties of the molecules that perform muscle movements as different as weight lifting and the peristaltic movements of the gut.
Demonstrations
A break for refreshments was followed by visits to laboratories to see demonstrations of practical procedures used in bio-medical research, ranging from physical techniques to the micro-injection of frog eggs:
- From egg to embryo with frogs, chicks and mice
- Images of biological material: transmission and scanning, electron microscopy, confocal light microscopy
- X-ray crystallography: molecular structure from X-ray scattering
- Large scale culture of bacteria and animal cells
- Mass spectrometry: determining molecular structure from fragments
- Nuclear magnetic resonance spectroscopy: molecular structure from magnetism
- The FACS machine: a method of physically sorting different cell types using fluorescence
- Electronic access to scientific information
Quiz and discussion
The demonstrations were followed by a quiz, and the afternoon finished with a discussion panel comprising scientists from the Institute who addressed questions the students raised, bringing to an end another successful Schools Day.
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