Nick Hoogenraad, Executive Director of the University’s new La Trobe Institute for Molecular Science, has joined a select group of top researchers whose life stories have been filmed and recorded by the Australian Academy of Science.
In its ‘Interviews with Australian Scientists’ series, Professor Hoogenraad discusses his work, probing ways in which mitochondria – highly specialised biological structures that act as the ‘power house’ of cells – communicate with, and affect the development of our cells.
Achievements in his lab over more than three decades into understanding the formation and function of mitochondria support the fight against mitochondrial diseases. These range from genetic disorders called ‘inborn errors of metabolism’ in newborn children, to diabetes, obesity and cardiovascular problems. Mitochondrial processes are also integral to ageing and cell death.
His research team has made significant contributions to the discovery of ‘biomarkers’, biochemical features on the surface of cells, that can be used to diagnose diseases, measure their progression and the effects of treatment.
Biomarkers also serve as therapeutic targets for monoclonal antibodies, ‘magic bullets’, directed by modern medicine against diseased cells such as cancer cells.
The man, as well as his science
Professor Hoogenraad joins a select group of 130 distinguished scientists of several generations, including physiologist Sir Rutherford Robertson, Antarctic researcher Dr Phillip Law (also a member of La Trobe’s founding Council) and immunologists Sir Gustav Nossal and Professor Peter Doherty, who appear in the Academy’s interviews.
Cecily Oakley, who manages the interview program, says the video also highlights the man and what turned him into a scientist.
‘His career path has not always been smooth sailing. At age fifteen he ran away to sea,’ she says. ‘But he returned three months later to finish his studies, grow a beard, become an anti-war activist and fall in love with biochemistry – and his wife, Joan.’
Mitochondria, explains Professor Hoogenraad, are very tiny organelles essential for the viability of all cells, converting the energy of the food molecules we eat into the chemical energy for all living processes.
Mammalian cells must have the right amount of mitochondria to provide the chemical energy cells need to perform their functions. The amount of mitochondria varies depending on the energy requirements of the cell.
‘Human mitochondria have between 1,000 and 1,500 different proteins,’ he says ‘encoded by a subset of the 30,000 genes in the nucleus of each cell.’
His interest is in how a cell co-ordinates the activities of so many genes. Is there some kind of ‘master switch’ which controls all these genes? That’s the holy grail of his research. ‘We use both laboratory-based molecular genetics and a computational approach to examine a large number of genes encoding mitochondrial proteins to try to find some unifying information by which this control mechanism may occur.’
Escape from violent struggle
Born in The Hague, Holland, in 1942 during World War Two, Professor Hoogenraad later spent part of his childhood in Indonesia.
He recalls bullets whistling through his house during that nation’s struggle for independence, migrating to Australia in 1952. He graduated from the University of Melbourne with a PhD in Biochemistry in1969 and went on to postdoctoral work in the Department of Paediatrics at Stanford University, becoming assistant professor in Human Biology.
He returned to Australia in 1974. In La Trobe’s then newly established Department of Biochemistry, his lab immediately began building on his earlier work – leading to the important discovery that a large complex consisting of molecules called ‘chaperones’ transports mitochondrial proteins to the mitochondria where they can be imported.
‘This complex is like a space shuttle that takes the protein from the ribosome, where proteins are made in the cell, to dock with a receptor on the mitochondria where it is “handed over” to the protein import pore.’
Proteins destined for the mitochondria have amino acid ‘address signals’ on them, says Professor Hoogenraad, which specifies to where they should be ‘delivered’.
‘There are receptors on the mitochondria that proof-read the signal and say: “Yes, you can come in”. Then the precursor protein is pulled in by machinery inside the matrix of the mitochondria.
‘When these proteins get inside, the signal peptide is cleaved off so that it can never leave again. It is now trapped inside.’
His research lab at La Trobe has achieved international recognition for work on this import mechanism and the role of ‘chaperones’ in this process – as well as for the discovery of a mitochondrial stress response mechanism essential to the proper function of mitochondria.
Championing a new way with science
Professor Hoogenraad’s other passion has been championing the development of the new La Trobe Institute for Molecular Science. The Institute’s new building is now under construction on the Melbourne campus, enshrining his philosophy about ‘vertical integration’ of science education.
‘By this I mean we should have not just researchers and post-graduate students, but also the best undergraduate students. That way they can start to get a feeling for what it is like to work in a research lab in a research environment.
‘Also, we have an obligation to help with the education of kids before they come to university. In universities we are only too ready to complain about the quality of students we get in, and to complain about the curriculum that students are taught – but we have rarely seen it as our responsibility to make a contribution.’
Note: Other La Trobe scientists who feature in the Academy’s ‘Interview’ series are geneticist Professor Jenny Graves who rejoined the University this year from the ANU; physical chemist Professor James Morrison; botanist Professor Alan Wardrop and zoologist, Dr Patricia Woolley.
Read the transcript of the full interview here.
A DVD of the interview is also available from the Academy for $15.