Allure of Living Light

The unborn hero, the ‘Brainbow’ed mouse, the genetic marker that tracks cancer cells - GFP’s Fame. 

By Abdulrazak Adam Hassan, July 26, 2017

Fireflies and some jellyfish glow. Luminescent mushrooms, the Hawaiian Bobtail Squid - many living things - mostly marine - emit florescent shine. Quite mesmerizing to me and to many others.

Could this luminescence be a vital biomarker? Can it be used routinely? Can it help humanity?

I am a final year medical laboratory student and my innate curiosity led me to Nobel Laureate Professor Martin Chalfie’s lecture on ‘Green Fluorescent Protein (GFP): Lighting Up Life’ conducted in Dubai in March last year. The title of his lecture said it all.

Nobel Prize winner, Osamu Shimomura holding up a tube of the Green Fluorescent Protein GFP

Source: Nobel Prize

First photoprotein and the worm prize

In his lecture, Prof. Chalfie talked of Japanese marine biologist Osamu Shimomura’s  discovery of the first photoprotein - the scientist with whom he and Roger Yonchien Tsien shared the $1.4 million Nobel Prize for chemistry in 2008.

Shimomura appropriated the jellyfish, Aequorea Victoria, from Friday Harbour at Washington State in February 1962, and discovered a protein that shines blue in sea water along the edge of this jellyfish’s umbrella. He named it 'Aequorin'. It also glows blue in the presence of calcium ions.

Aequorea jellyfish collected by O.Shimomura at Friday Harbor and GFP in a test tube that he purified from 20,000 Aequorea specimens. Credit: Tom Kleindinst

Along with this extraction and isolation of Aequorin, another green fluorescent protein composed of amino acids was also purified, converting Aequorin’s blue emission into green bioluminescence.

The trajectory of fame for this ‘Green Fluorescent Protein’, or ‘GFP’ for short, began three decades later. In 1992, world-class biochemist Dr. Douglas Prasher, cloned the GFP gene. The same arduous process of extraction and isolation of photoproteins by capturing 1000s of Aequorea Victoria jelly fish was no longer necessary. 

Informed about Dr. Prasher’s GFP cloning, Dr. Chalfie collaborated with him and revolutionized biomedicine. He inserted GFP into the transparent ringworm C. elegans successfully, colouring six individual cells, enabling them to be tracked.

GFP’s glowing fame

The truth is that even after chemotherapy, cancerous stem cells remain inside the cancer patient. A research team at the University of Salford used the harmless bioluminescent GFP marker to label and “light up” cancer stem cells, otherwise invisible, circulating in the patient’s blood sample and track them.

They found that these stem cells spread to distant organs and can grow new tumours during the ‘metastatic’ stage of cancer. ScienceDaily reported their conclusion that contrary to the accepted view, cancer stem cells are at the heart of the regrowth of new malignant tumours. 

Nerve cells micrograph labeled with GFP- the evidence of use in living tissues captured by Henriette van Praag and Linda Kitabayashi 

GFP shows the unborn hero

GFP’s fame in medical science is attributed to its great potential in clinical research. 

Dr. Hina Chaudhry, a developmental geneticist with expertise in stem cell biology and her research associates at The Mount Sinai Hospital in New York, USA knew that in any demographic, pregnant women incurring a heart attack are most likely to survive. The hypothesis was that the pregnant woman’s heart sends out a message that reaches the foetus in her womb. Some foetal stem cells respond by moving up to the mother’s heart to fix the injured cardiac tissues.

The proof came when a wild female mouse without any ‘marker’ fluorescent cell was mated with a mouse whose cells were marked with GFP. When induced with a heart attack, the pregnant mouse survived, completing the normal term of pregnancy and delivering a mouse marked with GFP cells. After the delivery, observations showed increased rates of GFP where cardiac tissues had suffered injury in the pregnant mouse. Stem cells of the unborn foetus saved the mother’s life.

The ‘Brainbow’ed mouse

So much has happened. Roger Y. Tsien, who shared the Nobel Prize with Shimomora and Chalfie developed many variants of GFP to make it glow at slightly different wavelengths, creating tags of a brighter green, cyan, yellow and blue. Mikhail Matz and Sergei Lukyanov discovered six GFP-like proteins in fluorescent corals, including a red protein called DsRED. 

Then came the mapped mouse brain. Harvard Brain Center researchers Jeff Lichtman and Joshua Sanes used different colour tags derived from GFP to 'brainbow' the mouse. Can such tagging unravel solutions to neurodevelopmental disorders like autism, dementia, Altzheimer’s and Parkinson's disease? 

It remains to be seen. 

Strategies: Malaria and Diabetes

Given this genetic engineering potential, the latest strategy suggested to tackle malaria, the world’s most deadly parasitic killer in tropical and subtropical areas, is to tag sterile male mosquitoes with a GFP variant for easy detection, and release them in high risk malaria regions to limit mosquito reproduction.

Can GFP help type 1 diabetes patients? The race is on to find out whether cell therapy can engineer tissues of a patient’s own somatic cells to secrete insulin.  Liver cells have been engineered to do this. What next?

GFP opens the doors wide.

- excerpt from ‘Osamu Shimomura - Biographical’ - The Nobel Prizes 2008, Editor Karl Grandin, [Nobel Foundation], Stockholm, 2009

Acknowledgments

I wish to express my sincere thanks to Dr. Amal Al-Haddad, Visiting Professor at the Department of Health Sciences, Al Khawarizmi College for sharing expertise on the recent trends of GFP, its clinical research uses and her continuous encouragement.

My gratitude also goes to Faruk Sarkinfada PhD, Professor of Medical Microbiology at the Department of Health Sciences, Al Khawarizmi International College for the counselling and professional advise throughout this article.

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