The winner of the $25,000 Centenary Institute Lawrence Creative Prize will be announced on Tuesday 11 November during a lunchtime reception at UBS in Sydney.
“It’s a small step towards recognising that the most creative medical research is usually done by researchers early in their career—at a time when it’s hardest for them to secure funding,” says Centenary Executive Director, Professor Mathew Vadas AO.
The three finalists (in alphabetical order) are:
How a piece of mobile DNA could change your mind
A/Prof Geoff Faulkner of the Mater Research Institute in Brisbane thinks the differences in the way each human brain functions could be determined by a segment of mobile DNA known as L1.
L1 has the capacity to insert itself into the genome of individual brain cells. Just how many L1 sequences are inserted and where they occur is unique to each brain cell and may determine how it operates. Showing the impact of this is the subject of Geoff’s Lawrence Creative Prize proposal. If he’s right, it could have significant consequences for our understanding of memory and of brain disorders such as schizophrenia.
Cellular decisions that affect behaviour
Dr Lucy Palmer from the Florey Institute of Neuroscience and Mental Health in Melbourne wants to know how brain cells in mammals process and integrate the information they receive from the sensory environment and how this information impacts on animal behaviour.
She has been working on the neurons in the rodent brain which receive sensory information from their hind limbs, and has shown that a lot of processing occurs in the dendrites, the long filaments of the cells where information is received. Now she wants to determine how the decisions a cell makes—to pass on information or not—affects what an animal does.
Dr Nicolas Plachta from the Australian Regenerative Medicine Institute and EMBL Australia at Monash University is working on developing better and simpler ways of determining the health of the embryos to be implanted in IVF. And he does so by learning more about the very early stages of embryonic life.
Nico has already developed special microscope technology which allows him to study in single living embryonic cells the movement of individual molecules. This has enabled him to determine how the cells making up the embryo differ from those which form the placenta. And he has also documented shape changes in cells which signal the health of early embryos. He now wants to continue that work looking for other molecular and cellular signs of embryo health, and studying the possibilities for medical intervention.
More on each of the finalists below.
About the Lawrence Creative Prize
The Centenary Institute Lawrence Creative Prize is an exciting initiative to promote medical research in Australia and recognise the young talent that already exists in the field.
The Prize is awarded for creative biomedical research excellence in its broadest definition, including trans-disciplinary research.
It is marked by a perpetual hand blown glass trophy by Nick Mount, with a smaller replica for the winner. In 2014, $25,000 will be awarded to the winner to be equally split between a personal award and as support for a project or scientific travel.
“Exceptional young scientists can be hard to keep in Australia and we hope this award will not only celebrate their achievements but also encourage a domestic culture of brilliance in this truly important field,” says Centenary Institute Executive Director, Professor Mathew Vadas AO.
Sponsors of this year’s Centenary Institute Lawrence Creative Prize are: STW Group, Val Morgan Cinema Network, UBS and Deloitte.
About the Centenary Institute
The Centenary Institute of Cancer Medicine and Cell Biology is one of the leading independent medical research institutes in Australia. It strives for creativity and excellence in discovering improved diagnostics, treatments, and cures for cancer, inflammatory and cardiovascular diseases.
The Centenary is focused on understanding disease mechanisms and using this to develop interventions with clinical impact.
More at: www.centenary.org.au
More about the finalists
How a piece of mobile DNA could change your mind
A/Prof Geoff Faulkner of the Mater Research Institute in Brisbane thinks the differences in the way each human brain functions could be determined by a segment of mobile DNA, known as L1, which has the capacity to insert itself into the genome of individual brain cells. His work may have consequences for how memories form, for brain disorders such as schizophrenia, and even spills over into diseases such as haemophilia, muscular dystrophy and some forms of cancer.
While you may have never heard of L1 (long interspersed nuclear element 1), it is a large piece of you. In every genome in every cell in your body there are about half a million copies of L1. They represent about 17 per cent of your genome. “All except about 100 of them are fossils,” says Geoff. “They are faithfully reproduced every time a cell divides, but have few known functions.”
But the 100 active segments of L1 have an unusual ability. During cell division, copies of L1 can jump about and insert themselves into other places in the genome. In some cases they inhibit or destroy the activity of the gene where they land. Sometimes this alters the behaviour of a cell—and the process has been implicated in cancer and more than 100 other diseases. As this is most likely to happen in embryos and active sites of regenerative cells in adults, clumps of cells with differing L1 insertions can arise in these places, making the DNA a genetic mosaic.
Geoff has been studying the impact of L1 insertions in the hippocampus, the region of the brain involved in memory and an active site of cell division into adulthood. It turns out that as neurons mature in the hippocampus there comes a point where a compound which inhibits the activity of L1 is turned off, making hippocampal neurons particularly susceptible to L1 insertion. About four years ago Geoff teamed up with the pharmaceutical company Roche to develop a means of distinguishing active L1 segments from the fossils. Using this technique, along with a newly-developed method to sequence the genomes of individual neurons, he has found that there is indeed a high level of L1 insertions in the hippocampus, amounting to an average of 14.2 additional L1 copies per genome, making every neuron genetically unique.
So now he wants to see what impact this level of L1 insertion has. First, he and his research team are investigating whether patients with neurological disorders have more or fewer genes mutated by L1 insertions than normal. Already there is evidence that people with schizophrenia have substantially more insertions. Second, he wants to check if the level of L1 insertion affects learning. As L1 mobility depends on the same sort of reverse transcriptase enzyme as HIV, the cocktail of drugs used to treat that disease also inhibits L1. It can therefore be used to check if interfering with L1 and producing fewer insertions affects the capacity to learn, initially in mice.
Meanwhile, Geoff’s work has been noted internationally. Groups worldwide are beginning to use his techniques to check L1 impact on diseases elsewhere in the body. And the US National Institutes of Health has established a special fund to finance research into DNA mosaicism in neurons.
Cellular decisions that affect behaviour
Dr Lucy Palmer from the Florey Institute of Neuroscience and Mental Health in Melbourne wants to know how brain cells in mammals process and integrate the signals they receive from the sensory environment and how this information impacts behaviour. “The more we understand about the role such brain cells play, the better we will understand conditions such as brain trauma and stroke,” Lucy says.
Lucy has been studying the activity of brain cells by recording signals from the pyramidal neurons in the cortex of mice which receive sensory information from their hind limbs. Initially, she concentrated on the long filamentous neuronal extensions known as dendrites which is where signals are received. Using an intricate experimental recording technique, she was able to show for the first time in living cells that when the sensory signals reached a certain threshold, the pyramidal neurons fired off a much larger pulse known as a dendritic spike. In other words, they were processing the information as it came in, and only certain signals were passed on.
She also investigated the dendritic response to the sensory information sent when the hind limbs of the mouse were stimulated. You might expect a different response from stimulating two limbs as opposed to one but, interestingly, Lucy found that the second limb does not add to the signal from the first, but inhibits it. In fact, the signal was only one third as great when both feet were stimulated. And the magnitude of the signal also varies depending on which limb is stimulated first.
“The results from these investigations are far reaching and demonstrate the sort of adaptive changes that might occur in diseases that lead to disruptions in sensory perception such as stroke, traumatic brain injury, epilepsy, schizophrenia and alcoholism,” Lucy says. “The work also highlights potential targets for drug therapy for these debilitating diseases.”
Now she wants to see what impact such cell processing has on animal behaviour. For instance, if you train a mouse to expect food when you stimulate its senses in a particular way—by playing a tone or stroking some part of its body—a certain neuronal processing pattern will be established. What happens if you then block the dendrites receiving the stimulus? How will that change the animal’s behaviour?
Sorting out healthy embryos
Dr Nicolas Plachta from the Australian Regenerative Medicine Institute and EMBL Australia at Monash University wants to develop better and simpler ways of determining the health of the embryos to be implanted in IVF. And he does so by learning more about the very early stages of embryonic life. “Having the ability to screen IVF embryos for defects before introduction to the uterus would greatly reduce the expense and trauma of IVF,” he says. “It would minimise the need for terminations or expensive re-attempts.”
Whether an embryo is healthy or not depends on the decisions its component cells make about which type of cell they will grow into and with what other cells they will associate. So the information Nico needed to determine the health or otherwise of embryos had to be information based on the behaviour of living embryonic cells and the movement of molecules within them. But the microscope imaging equipment to allow him to gather such information in live embryos did not exist when he began his work.
So his first job was to develop a new microscope technology he named photoactivatable fluorescent correlation spectroscopy that could be used to track fluorescently-tagged biomolecules over time in live mouse embryo cells.
Initially, he observed the behaviour of transcription factors, the compounds that oversee the process of translating the genetic blueprints encoded in the DNA into a form which can be used to generate proteins. These compounds are critical to the healthy operation of embryonic cells. But they function in all cells, including neighbouring cells that will not be incorporated into the embryo, but will become part of the placenta instead.
Nico soon discovered these two types of cell could be told apart by the behaviour of their transcription factors. In the embryo the transcription factors bound more tightly to the DNA and at different sites from those in cells destined for the placenta.
As the embryo developed, Nico also observed shape changes in its cells. In particular, at the eight-cell stage the cells draw together and compact, during which time their shape changes from round to elongated. Then they relax back to their round shape and begin to divide again. But the compaction stage is essential for embryo survival, Nico and his colleagues found, and it is engineered by arm-like structures called filopodia which emerge from the outer membrane of about half the cells.
Nico is convinced there is plenty more to discover about what happens at the early embryo stage, and what makes a healthy embryo. He is busy looking for other molecular and cellular signals of embryo health, and is also investigating the possibility of passive medical intervention to nudge embryos along the right developmental path.