Glowing jellyfish protein sheds light on human disease

 

Challenge: see the inner workings of a cell

Natural inspiration: Crystal jelly Aequorea victoriaCrystal jelly lit by flash. © Anky10/Dreamstime

 

 

 

For most of medical history, scientists have not been able to study living cells in action.  Methods of preparing cells for examination under a microscope involved killing them: the researchers could study static structures but not how substances moved around within the cell when it was functioning. The answer to this problem came from small jellyfish found off the west coast of North America, commonly known as crystal jellies.

 

 

 

 

 

Green fluorescent protein © Dr Steve Haddock, http://lifesci.ucsb.edu/~biolum/

Crystal jellies are bioluminescent:  they produce their own light.  The light appears as intermittently glowing green dots around the edge of the animal's 'bell', and its function in nature is not yet fully understood. 1  In 1962, a team of scientists collected jellyfish and managed to isolate the protein that caused the glow. 2  In 1992 the gene for this Green Fluorescent Protein (GFP) was sequenced 3, and finally in 1994 scientists succeeded in inserting the GFP gene into other cells to make them glow. Since this achievement, GFP has become a valuable tool for geneticists and other scientists.  It can be attached to other proteins in living cells, acting as a marker to show their movements.  In the last few years, scientists have found how to make proteins that glow different colours, allowing them to study more complex processes and structures including brain tissue. 5  In 2008, the Nobel Prize for Chemistry was awarded to the three pioneers of GFP research, an indication of the importance of the discovery.

 

smiling elderly man © Hector Landaeta, www.sxc.hu

 

 

As well as advancing basic knowledge of how cells work, 6 GFP has made possible many medical breakthroughs, including a better understanding of how cancer spreads 7 and of what causes Alzheimer's disease 8.  An estimated 35 million people globally have Alzheimer’s disease or other forms of dementia, and this number is forecast to increase significantly, particularly in developing countries. 9  In the UK alone, dementia costs the economy £23 billion per year. 10 If scientists could develop a treatment that would reduce the illness in older people by just 1% per year, this would  cancel out all estimated increases in the long-term care costs due to the world’s ageing population. 11

 

 

 

woman using microscope © Imagez/ Dreamstime

GFP has also helped in the fight against malaria by making it possible to separate out male and female mosquito larvae. 12  Malaria is one of humanity’s major diseases.  Around 1 million people die of malaria every year, the majority of them African children.  As well as the human toll, malaria has a significant economic effect, decreasing Gross Domestic Product (GDP) by as much as 1.3% in the worst-affected countries.  Malaria may account for up to 40% of public health expenditure in these places. 13  Malaria is transmitted to people by mosquitoes.  Releasing sterile male mosquitoes into the wild is a very effective way of controlling the mosquito population and thus reducing the number of malaria cases: a female mosquito that mates with a sterile male has no offspring.  Releasing sterile females does not help to control the population, so being able to easily separate out the males for sterilisation is a vital step. 12  Mosquitoes can now be genetically engineered to produce GFP in their sexual organs, allowing the males and females to be easily told apart even as larvae. 12

 

Jellyfish © Zando Escultura, www.sxc.hu

 

All these advances were made possible by biodiversity.  The crystal jelly is an excellent example of how any seemingly insignificant organism could hold the key to a breakthrough.  Crystal jellies are in the class of organisms called hydrozoa.  There are about 3,500 species of hydrozoa, with a huge variety of body forms and life histories. 14 Crystal jellies are currently abundant in their home range, although some researchers have noticed a drop in their numbers in recent decades, for reasons unknown. 1 If the species really is in decline, it is fortunate for humans that we discovered its secret before it disappears altogether.

 

 

 

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References

  1. University of Washington: Bioluminescence and other factoids about Aequorea, a hydromedusa.  Accessed March 2010.
  2. Shimomura, O. et al (1962)  Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan Aequorea. Journal of Cellular and Comparitive Physiology 59, 223-239
  3. Prasher, D.C. et al. (1992) Primary structure of the Aequorea victoria green-fluorescent protein. Gene 111: 229-233.
  4. Chalfie, M. et al. (1994) Green fluorescent protein as a marker for gene expression.  Science 11:802-5.
  5. Livet, J. et al. (2007) Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system.   Nature, doi:10.1038/nature06293.  See the full article with colour pictures. Accessed March 2010.
  6. Lippincott-Schwartz, J. et al. (2003) Development and Use of Fluorescent Protein Markers in Living Cells. Science 4: 87 - 91
  7. Chishima, T. et al. (1997) Cancer Invasion and Micrometastasis Visualized in Live Tissue by Green Fluorescent Protein Expression.   Cancer Research 57: 2042-2047. Full article available online.  Accessed March 2010.
  8. Bence, N.F. et al. (2001) Impairment of the Ubiquitin-Proteasome System by Protein Aggregation. Science 25: 1552 – 1555
  9. World Alzheimer Report 2009 (executive summary).  Accessed March 2010.
  10. The Alzheimer’s Research Trust: Dementia 2010 Accessed March 2010.
  11. Comas-Herrera, A. et al (2007) Cognitive impairment in older people: future demand for long-term care services and the associated costs.
  12. Catteruccia, F. et al. (2005) An Anopheles transgenic sexing strain for vector control.  Nature Biotechnology 23: 1414 – 1417.  Full article available online.  Accessed March 2010.
  13. World Health Organisation malaria factsheet.  Accessed March 2010.
  14. Museum of Geneva: The Hydrozoa directory,   Accessed March 2010.

 

Further reading
Green Fluorescent Protein – web page from Conneticut College chemistry department.  Accessed March 2010. 
Glowing jellyfish grabs Nobel, BBC News, October 2008.  Accesed March 2010.
A guiding glow to track what was once invisible, New York Times, October 2008.  Accessed March 2010.