Programmed cell death

Research into the life and times of a worm that lives in soil and rotting vegetation has won three scientists a share of ten million Swedish Kroner (about £690,000) in this year’s Nobel Prize for Medicine. Sydney Brenner worked in Cambridge during the 1960s and did the groundwork for modern biological science. He recognised that a lowly worm could help us understand how cells live and die. His work on the nematode Caenorhabditis elegans has provided researchers with a living model of how cells in organisms mature, differentiate, operate and die.

The body of the nematode worm and our own bodies consist of many different cell types, all originating from a single fertilized egg, which rapidly divides during embryonic development. As the embryo grows its cells mature and begin to specialize, or differentiate, into their different functional forms building up the different tissues and organs in nematode and human alike.

Sydney Brenner

Sydney Brenner

Working in parallel with these growing processes is a third process known as programmed cell death, or apoptosis. Cell death culls unwanted or damaged cells, hollowing out balls of cells to make chambers and vessels, and separating out once-webbed fingers and toes.

Brenner’s masterstroke was to link the analysis of the nematode’s genes with the essential life processes of cell division, differentiation and organ development. John Sulston of The Wellcome Trust Sanger Institute in Cambridge, England, extended this research by mapping every cell division and differentiation in the nematode to every tissue. He showed that specific cells undergo apoptosis. He went on to identify the first genetic mutation inherent in apoptosis.

The Horvitz worm - a C. elegans embryo in which all cells have been caused to initiate programmed cell death (apoptosis). (Image: Brad Hersh and H. Robert Horvitz)

The Horvitz worm – a C. elegans embryo in which all cells have been caused to initiate programmed cell death (apoptosis). (Image: Brad Hersh and H. Robert Horvitz)

Robert Horvitz of the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts, USA, also built on Brenner and Sulston’s work finding several key genes involved in apoptosis. He figured out how they interact and identified their human counterparts. All three men paved the way for a better understanding of cell processes, which ultimately improve medicine’s approach to diseases such as cancer.

John Sulston

John Sulston

Robert Horvitz

Robert Horvitz

Further reading

Sydney Brenner
http://www.salk.edu/faculty/faculty_details.php?id=7

Wellcome Trust Sanger Institute
http://www.wellcome.ac.uk/Achievements-and-Impact/Initiatives/UK-biomedical-science/Genome-Campus-and-Sanger-Institute/WTD003479.htm

Robert Horvitz
http://www.hhmi.org/research/investigators/horvitz.html

Suggested searches

Nobel prizes

All material in this article is © David Bradley Science Writer and Intute and may not be reproduced without express permission.

Shedding spectral light on giant molecules

Research that laid the foundations for research as diverse as understanding cancer, prion diseases, and malaria as well as offering hope of faster diagnostics and improved food quality control has been awarded this year’s Nobel Prize for Chemistry.

John Fenn of Virginia Commonwealth University, Richmond, USA, and Koichi Tanaka of the Shimadzu Corporation, Kyoto, Japan, share half the 10m Swedish Krona prize for their work on methods of suspending proteins and other macromolecules, such as polymers and nucleic acids, for analysis by mass spectrometry.

John Fenn

John Fenn

Mass spectrometry can be used to determine the mass of a molecule or indeed fragments of that molecule. Fenn began work on devising a method for suspending proteins in a mass spectrometer in the 1980s. Until that time mass spectrometry was only really useful for small molecules with a limited number of atoms not the vast macromolecules of nature, such as proteins, which can have hundreds and thousands of atoms.

Fenn’s method of electrospray ionisation (ESI) was based on spraying droplets of protein solution with an electric field and allowing the solvent in which they were dissolved to evaporate. This process left stark, naked protein ions hanging in the chamber of his mass spectrometer ready for analysis.

Koichi Tanaka

Koichi Tanaka

Tanaka, meanwhile, had discovered that a pulse of laser light could blast a viscous sample of protein into separate charged molecules. Once in this form, he used an electric field to accelerate the ions across the mass spectrometer’s chamber. He could then build up a spectrum of the original protein molecule based on the differences in the times of flight recorded for each electrically charged fragment.

Protein structure

Protein structure

Many sensitive mass spectrometry techniques, such as MALDI (matrix-assisted laser desorption ionisation), emerged following this pioneering work.

Kurt Wüthrich

Kurt Wüthrich

While Fenn and Tanaka provided scientists with a way to find out what protein they had in a sample and how much, their work said nothing of what that protein looks like – its three-dimensional molecular structure, in other words. That was down to the work of the winner of the other half of this year’s chemistry Nobel – Kurt Wüthrich of the Swiss Federal Institute of Technology, Zürich), Switzerland.

Kurt Wüthrich talks about the protein structure

Kurt Wüthrich talks about the protein structure

Wüthrich developed a way to assign each signal in a proton nuclear magnetic resonance spectrum to the appropriate hydrogen atoms – and there are many of them – in a protein. A comparison of the distances between pairs of peaks in the spectrum could then be used to build a picture of where they all fit in the structure. This information can then be used to generate the protein’s all-important three-dimensional structure.

Another view of the protein

Another view of the protein

The technique works on proteins in solution so, unlike X-ray crystallography, does not require a crystalline form to be made first. The method even solves proteins working in living cells. Since the invention of the method in 1985 hundreds and hundreds of the thousands of known protein structures have been determined by NMR.

Further reading

John Fenn
http://www.has.vcu.edu/che/people/bio/fenn.html

Shimadzu Corporation
http://www.shimadzu.com/

Kurt Wüthrich
http://www.mol.biol.ethz.ch/wuthrich/people/kw/

Suggested searches

Nobel prizes
Electrospray ionisation
Proton NMR spectroscopy
Protein structure

Universal views

Cosmic neutrinos and X-rays from space netted this year’s physics Nobel Prize winners their share of the 10 million Swedish Kroner prize (almost £700,000). Half of the prize money was shared between Raymond Davis Jr of the University of Pennsylvania, Philadelphia, USA, and Masatoshi Koshiba of the University of Tokyo, Japan, for their research which plumbed the depths of the earth to detect neutrinos from space. The other half went to Riccardo Giacconi, President of Associated Universities, in Washington DC, USA, who created a new astronomical window of opportunity transparent to X-rays.

The tiny elementary particle known as the neutrino was first predicted in 1930 by Nobel physicist Wolfgang Pauli. He realised an uncharged and massless particle was needed to balance the books in radioactive beta decay. It was another 25 years before its existence was proven by Nobel laureate Frederick Reines and Clyde Cowan. It was realised that if the Sun was powered by nuclear fusion rather than gravity, then it would release neutrinos in unimaginable numbers. However, detecting a particle that passes unnoticed through matter is tough.

Raymond Davis

Raymond Davis

Davis installed a gigantic tank of 615 tonnes of dichloromethane at the foot of a mineshaft away from cosmic interference. The chlorine atoms were the key to detecting neutrinos. When a neutrino hits a chlorine atom, radioactive argon is produced. The chance of a collision make winning the lottery look a dead cert but wait long enough and the telltale signs of radioactive argon would ultimately be detected.

Over a period of thirty years Davis’ tank has captured 2000 Solar neutrinos, proving that the Sun is powered by hydrogen fusion.

Masatoshi Koshiba

Masatoshi Koshiba

Koshiba subsequently used a similar detector to confirm Davis’ results. He and his colleagues went a step further though. On 23 February 1987, their detector captured twelve neutrinos from a distant supernova explosion. That is a tiny fraction of the 10,000,000,000,000,000 (1016) that passed through the detector.

The tank!

The tank!

The Sun and all other stars emit electromagnetic radiation at different wavelengths, as well as neutrinos. Visible light and ultraviolet have particular wavelength ranges, while X-rays have another. The problem for astronomers on earth is that X-rays are absorbed by the atmosphere; thankfully you might say from a health perspective.

Davis and the tank

Davis and the tank

To observe cosmic X-ray sources an instrument has to be put into space from where it can send back a signal to astronomers on Earth.

Riccardo Giacconi

Riccardo Giaccon

Giacconi constructed such an instrument in the 1960s and detected the first source of X-rays outside our Solar system. His findings showed that the Universe has a background radiation of X-rays. He also spotted X-rays coming from regions of space that most astronomers believe contain black holes.

Another look at Riccardo Giacconi

Another look at Riccardo Giacconi

Further reading

Raymond Davis Jr
http://www.bnl.gov/bnlweb/raydavis/research.htm

Riccardo Giacconi
http://physics-astronomy.jhu.edu/people/faculty/giacconi.html

Wolfgang Pauli
http://nobelprize.org/nobel_prizes/physics/laureates/1945/pauli-bio.html

Frederick Reines
http://nobelprize.org/nobel_prizes/physics/laureates/1995/reines-autobio.html

Suggested searches

Nobel prizes
Neutrino detectors
Neutrinos
X-ray astronomy