 Dr
Stephen Nutt
Dr Stephen Nutt is an immunologist interested in understanding the processes that control the differentiation of the rare haemopoietic stem cell into the specific blood cell lineages. He is currently the inaugural Metcalf fellow and a laboratory head in the Immunology Division of The Walter and Eliza Hall Institute of Medical Research.
Prior to beginning his academic career Dr Nutt spent a period in the biotechnology industry in Toronto, Canada at Allelix Biopharmaceuticals Inc. He then carried out his postgraduate studies at the Research Institute of Molecular Pathology (Vienna, Austria) under the guidance of Professor Meinrad Busslinger. This graduate research demonstrated the pivotal role that the transcription factor Pax5 plays in the B cell differentiation, and resulted in the seminal finding that Pax5 directs the commitment of haemopoietic progenitors to the B cell lineage. The initial two publications describing this research have been cited a combined 440 times since 1999.
Dr Nutt then undertook post-doctoral training in the laboratory of Dr Amaya at The Wellcome Trust/CRUK Gurdon Institute of Cancer and Developmental Biology (Cambridge, UK) where he examined the important role played by FGF-signalling in the patterning of the early vertebrate embryo, using Xenopus laevis as a model system. This research was supported by prestigious European Molecular Biology Organization (EMBO) and Human Frontiers Scientific Program (HFSP) Fellowships.
Dr Nutt returned to Australia in 2001 and has instigated a broad and ambitious research program that involves many aspects of haemopoiesis and has generated a number of new mouse transgenic models to facilitate the research. This research has focused on a number of so-called “master-regulatory” transcription factors, including Pax5, PU.1 and Blimp-1 that are thought to be instrumental in controlling haemopoiesis. Recent studies have highlighted the essential role of PU.1 in the early differentiation of the stem cell to more committed progenitors. He has also identified the transcriptional repressor Blimp-1 as being a conserved regulator of the final stages of lymphocyte differentiation essential for protective immunity. Dr Nutt has authored more than 40 publications in the highest-ranking international journals, holds numerous patents and has many collaborators within Australia and abroad.
Dr Nutt has been funded by several NHMRC and Cancer Council Victoria project grants and is currently a chief investigator on an NHMRC program grant (with Drs Hodgkin, Tarlinton, Corcoran) aimed at understanding the production of antibody by the humeral immune system. Dr Nutt’s laboratory currently consists of 3 post-doctoral fellows, 2 PhD students and research technician.
During the Pfizer Australia fellowship Dr Nutt will use his expertise in the regulation of blood cell differentiation and his unique genetically modified mouse models to address the functions of these master regulatory transcription factors in normal development as well as in disease pathologies such as leukaemia and autoimmunity. An understanding of the key regulatory events that are deregulated in these mouse models will then guide future research into the equivalent human disease states. |
 Dr Anthony Hannan
Dr. Hannan is a neuroscientist whose main interests focus on gene-environment interactions and experience-dependent plasticity in the healthy and diseased brain. He is currently a Senior Research Fellow, supported by an RD Wright Career Development Award from the NHMRC, at the Howard Florey Institute, University of Melbourne. There he heads the Neural Plasticity Group, modelling disorders of brain development and plasticity, such as schizophrenia, Huntington’s disease, depression and dementia, as well as biological processes which regulate normal brain maturation and function.
Dr. Hannan received his undergraduate and PhD degrees from the University of Sydney, including graduate research training at the Children’s Medical Research Institute, Westmead. In 1996 he was awarded the Australian Nuffield Medical Fellowship to carry out postdoctoral research in the University Laboratory of Physiology, University of Oxford. In 2002, with the support of the NHMRC RD Wright award, Dr. Hannan returned from Oxford to set up his research group at the Howard Florey Institute.
In Oxford and Melbourne, one major focus for Dr. Hannan has been investigation of intracellular signalling pathways that regulate the way in which neurons are sculpted by experience in the postnatal cerebral cortex. The data from his laboratory suggests that a specific intraneuronal signalling pathway is necessary for the co-ordinated development of the cortex and that disruption of this pathway leads to abnormal cortical maturation and associated behavioural abnormalities, including cognitive deficits. Furthermore, ongoing research in Dr. Hannan’s laboratory has linked this signalling pathway to a number of genes recently implicated in the molecular pathogenesis of schizophrenia, a devastating disorder of brain development and function.
Huntington’s disease (HD) is one of many neurological disorders known to be caused by trinucleotide repeat expansions. The fatal disease is characterized by degeneration of the cortex and striatum, producing motor, cognitive and psychiatric symptoms. Dr. Hannan and his group have also investigated mechanisms of HD pathogenesis by altering levels of sensorimotor and cognitive stimulation in transgenic HD mice through environmental manipulations. Although HD was thought to be the epitome of genetic determinism, their recent work has demonstrated that environmental factors can modulate the disease process in transgenic mouse models. Environmental enrichment of transgenic HD mice was found by Dr. Hannan and his graduate students to dramatically delay onset and progression of motor symptoms. This was the first demonstration, in any transgenic animal model, that environmental stimulation can delay onset and progression of a brain disease.
Dr. Hannan’s group has used environmental manipulations as tools to dissect cause and effect amongst molecular and cellular correlates of HD pathogenesis. These results suggest that environmental enrichment benefits animals at early stages of the disease by rescuing transcriptional dysregulation of specific genes, and possibly also salvaging protein trafficking abnormalities. Dr Hannan and his colleagues have provided evidence that environmental enrichment may overcome deficits of synaptic plasticity and adult neurogenesis in HD mice, via effects on specific molecules, thus guiding development of novel therapeutics which mimic or enhance the beneficial effects of environmental stimulation (‘enviromimetics’). This will also have important implications for related brain disorders, such as Alzheimer’s disease.
The Pfizer Australia Research Fellowship will allow Dr. Hannan to further explore such key areas of neuroscience, and work towards the eventual development of new therapeutic approaches for these devastating brain diseases.
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