Dr Daniel Hesselson (centre) with Dr Nicole Schönrock and Dr Guy Barry
21 July 2014
Dr Daniel Hesselson has won the 2014 Young Garvan Award. The announcement was made on Saturday night at Young Garvan’s main annual fundraising event, the “All Ribbons Ball”, held this year at the Sofitel Sydney Wentworth hotel.
A volunteer group of young professionals, Young Garvan informs and inspires the younger generation about Garvan’s medical research. The Young Garvan Award is the main fundraising aim of the group, and provides $50,000 each year towards supporting an early career scientist.
This year, Dr Guy Barry and Dr Nicole Schönrock were also awarded a Special Initiative Award of $10,000 each.
Dan Hesselson set up a lab at Garvan in 2012, using zebrafish as a model to study human disease. Zebrafish are small (around 3 cm when fully grown), hardy, and easy to breed. They are also vertebrates, so their cells and organs are similar to those of mice and humans, making findings in the fish applicable to humans.
Dan’s $50,000 award will go towards a project using zebrafish to identify genes or drugs that might impede the progressive loss of dopamine-producing brain cells in Parkinson’s Disease (PD).
Dan has found that ‘Parkinson’s fish’ – fish genetically altered with known Parkinson’s mutations – are very sensitive to toxins that affect mitochondria, the energy-producing centres of cells, whose function is known to be disturbed in PD.
To simulate onset of PD in these fish, Dan will expose them to very low doses of the toxins (found mainly in pesticides), and then will try to find other genes or drugs to protect them.
As part of this project, Dan will collaborate with the Functional Genomics lab at Garvan to validate genes that protect dopamine neurons using a variety of model systems including flies and human cells.
Nicole Schönrock and Guy Barry are both in Garvan’s RNA Biology and Plasticity lab, and each will use their Special Initiative Award to further their work on separate projects.
Nicole Schönrock is exploring uncharted territory in the realm of RNA molecules – genetic material likely responsible for the complexity that makes us human.
Some aspects of RNA are well understood – its role in helping to make proteins, the building blocks of cells, for example. Most RNA does not code for protein, however, and we are only just beginning to understand some of its functions.
Language is the metaphor Nicole finds most useful to describe the complexity of RNA communication. We know very little about the RNA language, and we are still in the process of deciphering its alphabet. Some letters of that alphabet – to complicate things – are ‘decorated’ with marks that change its meaning, much like the accents used in several languages.
Nicole’s project is investigating the hundreds of modifications that decorate RNA molecules. In the same way as the ‘o’ in Schönrock is decorated with an umlaut to change its pronunciation, various chemical groups attach to RNA molecules to change their stability or function.
When RNA modifications become disrupted, cells can no longer function normally, leading to diseases such as cancer and intellectual disability.
Our understanding of this RNA lexicon and its grammar is still very primitive, and Nicole sees it as part of her mission to develop an RNA modification dictionary or thesaurus. Nicole will be using her Young Garvan award to sequence and identify two RNA modifications in the brain that lead to intellectual disability when disrupted.
Guy Barry will attempt to demonstrate that the modern Theory of Evolution is incomplete. The current paradigm, which has not been updated since 1942, incorporates Charles Darwin’s ideas on natural selection as well as the ideas of many other thinkers. Guy believes it needs an overhaul in the light of current knowledge. (See the paper on this topic that he published late last year in the Journal Frontiers in Neuroscience.)
The main problem, says Guy, is that prevailing dogma teaches that evolution is both gradual and random, yet many examples show this is not always the case. Children born to mothers who had lived through the Dutch famine of 1944, for example, were born smaller and more susceptible to diabetes and obesity. The post-war generation then passed those traits on to their children.
In some way, organisms constantly adapt to their environment, passing heritable knowledge to their offspring. Guy acknowledges this concept is not new (many thinkers, from pre-Socratic Greek philosophers through to Jean-Baptiste Lamarck and Darwin, have acknowledged its likelihood), yet the mechanisms involved have remained a mystery.
Guy has his own hypothesis, involving small RNAs being released from the body’s cells, and then making their way to reproductive organs and encoding change. His award will pay for an experiment using genetically modified mice to demonstrate this process beyond doubt.
He believes that the new paradigm would make humankind take greater responsibility for the immediate effects of its own lifestyle choices upon future generations.