October 31, 2016

The Future Belongs to the Curious

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What if Mendel never wondered about how pea plants inherited characteristics? What if Rosalind Franklin was never curious about the structure of the odd new molecule DNA? What if the Curies never asked how radioactivity worked? The world today would have been very different, indeed.

Barry Stoddard, the speaker at this week’s Seminar Series hosted by the Department of Molecular Biology and Genetics, emphasized this undeniable importance of curiosity in fuelling research. These series are held throughout the semester, bringing eminent scientists and their pioneering research to Cornell. The lecture, held on Oct. 28th in the Biotechnology building, saw a room packed with professors and students alike eager to hear about Dr. Stoddard’s research on Invasive Genetic Elements.

A senior researcher at the Fred Hutchinson Cancer Research Centre in Seattle and an affiliate professor at the University of Washington’s School of Medicine, Stoddard primarily researches how different biological structures and correlate with their functions at an atomic level.

His curiosity for understanding how things work at a micro-level in the cell led him to study Invasive Genetic Elements in genomes of yeast and phages amongst other single-celled organisms. Invasive Genetic Elements refer to gene sequences which propagate themselves by adding their sequence to genomes that lack it.

“Studying, comparing and contrasting the behaviours of both naturally evolved and engineered variants of biomolecular systems, any biomolecular system, is a very powerful approach,” Stoddard said.

Stoddard’s 20 years’ work on Invasive Genetic Elements focuses on natural and synthetic genetic sequences that code for ‘LAGLIDADG homing endonucleases’. These endonucleases are enzymes that cleave DNA in specific sites and propagate copies of themselves. These enzymes can invade a wide variety of genomes ranging from bacteria to plant genomes.

Nine such endonucleases were crystallised for further study and were looked at for structural characteristics and mechanisms that enable them to dominantly invade other genomes. As these were studied further, several facts about their structures, functions and strengths were assessed. One important conclusion was that the rate of disruption of the genomes is increased if a hybrid of two different enzymes were used.

This research opens up several avenues in genetic engineering and invasive genetics. For example, a potential lead for further research would be to engineer cells responsible for immunity by adding an invasive genetic sequence which will cause the cells to attack and destroy tumour cells. Another important implication for this in genome editing. Due to the high specificity of cleavage and diversity of genomes invaded, invasive genetic elements provide for an extremely efficient method for adding desired genetic sequences into genomes. Thus, Stoddard’s work has undoubtedly made major breakthroughs in the field of genetic manipulation and engineering.

He concluded with words that ring true for the entire scientific world.

“The entire history [of gene target endonucleases is] of which we have now enjoyed an embarrassment of riches was entirely founded by curiosity driven basic research.”

It is the sheer curiosity to learn about something where science has not gone yet that has inspired the scientists before him, that inspired his research, and will continue to inspire the scientists of the future.

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