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The Huntington Society is pleased to announce, as part of its 1999-2000 research programme, the first post-doctoral awards granted under the auspices of the NAVIGATOR initiative and our partnerships with the Medical Research Council of Canada (MRC) and the Canadian Genetic Diseases Network (CGDN).
The Huntington Society/Canadian Genetic Diseases Network Fellowship has been awarded to Edmond Chan, who will be working in the laboratory of Dr. Michael Hayden at the Centre for Molecular Medicine and Therapeutics in Vancouver. Chan�s project aims to identify changes in global gene expression that are correlated with the appearance of symptoms of HD. Using the new YAC (yeast artificial chromosome) transgenic mouse, which expresses a full-length version of the huntingtin protein, Chan will study brain tissue at three, six and 12 months of age, looking for changes which coincide with and may be linked to the onset of symptoms.
Although the huntingtin protein is expressed throughout the body, cell death occurs selectively -- suggesting that huntingtin is interacting with other proteins found in brain cells affected by HD. Working under the supervision of Dr. Harold Robertson at Dalhousie University in Halifax, Dr. Geraldine MacGibbon has been awarded the Huntington Society/Medical Research Council Fellowship. She will be using animal models to study gene expression in different types of neurons, work which will help to define the mechanisms that lead to cell death in Huntington disease.
In 1999-2000, John Rubinstein enters the second year of his Landmark Graduate Award. Working at the MRC Laboratory of Molecular Biology in Cambridge, England under the supervision of Dr. John Walker, winner of the 1997 Nobel Prize in Chemistry, Mr. Rubinstein is using electron microscopy to develop a three-dimensional model of �complex I� -- a mitochondrial protein which may be defective in cells affected by Huntington disease. Mr. Rubinstein�s project is generating important insights which could be relevant to the rational design of new drugs for the treatment of HD.
The Society�s Research Council has also recommended that HSC continue to support the Huntington Study Group, an important international collaboration which is achieving impressive results in the clinical investigation of HD. Recent highlights include the ongoing CARE-HD trial -- a multi-centre study designed to determine the potential efficacy of remacemide and/or co-enzyme Q10 -- and planning for a range of new studies, such as PHAROS and PREDICT-HD. (See Horizon, 88:1998)
The Society will also soon be announcing its first NAVIGATOR Research Award, and implementing other granting programmes which make up the NAVIGATOR initiative.
In short, this promises to be a very exciting year in the history of the Huntington Society�s support for the HD research effort.
Vik Chopra has held a Huntington Society pre-doctoral award since 1996, and his strong performance has been recognized by the Research Council with a third and final year of funding.
Under the supervision of Dr. Michael Hayden, Mr. Chopra's work focuses on a protein called HIP-1, or huntingtin interacting protein. As the name suggests, HIP-1 interacts with huntingtin, the protein produced by the HD gene, and an improved understanding of this compound may help to answer one of the central questions in HD research today: why does the defective version of huntingtin cause the selective death of brain cells?
In collaboration with other members of Dr. Hayden's group, Mr. Chopra has achieved significant progress in characterizing HIP-1, and he is now exploring some of the intriguing ideas which have been put forward about the relationship between HIP-1 and huntingtin. For example, it has been suggested that the interaction of these proteins may be central to the assembly and function of the internal structure which supports cells, called the cytoskeleton.
Having determined that HIP-1 is part of a family of genes, Mr. Chopra is working to isolate and analyze related genes in humans and in mice. His work will shed additional light on the normal function of HIP-1 and its relationship to the death of brain cells in Huntington disease, and may suggest new targets for therapeutic intervention.
In Dalhousie University's Department of Pharmacology, Matthew Hebb is producing important insights into the expression of the HD gene, and the possible role of the huntingtin protein in the normal adult brain.
Focusing on specific areas of the rat brain, Mr. Hebb has made the significant observation that production of the huntingtin protein seems to be increased, or up-regulated, in rats which have recently given birth -- suggesting that hormones may be linked to protein expression.
In addition, preliminary studies indicate that the huntingtin protein may be intimately associated with the chemical cascade which leads to cellular differentiation during early development.
Further insights will help us to understand more about the role of the HD gene in the central nervous system -- and perhaps how to block or circumvent the onset of the disease process.
Funded by the Huntington Society of Canada since 1996, Mr. Hebb is interested in pursuing his studies of Huntington disease at the post-doctoral level. His work has already encouraged his supervisor, Dr. Harold Robertson, to allocate increased laboratory time and attention to Huntington disease.
The discovery of the double helix structure of DNA, by Francis Crick and James Watson, is one of many scientific breakthroughs associated with the Medical Research Council Laboratory of Molecular Biology in Cambridge, England.
One of the outstanding scientists now working at this prestigious institution is Dr. John Walker, winner of the 1997 Nobel Prize in Chemistry and a Fellow of the Royal Society of London. Beginning this year, Dr. Walker will be supervising the work of John Rubinstein, recipient of the first Landmark Graduate Award to be granted through the NAVIGATOR programme.
Cell death in Huntington disease may be closely linked to dysfunction of a process known as electron transport. This process occurs in mitochondria -- the small structures that serve as the energy generators of cells. Although electron transport is crucial to the survival of cells, the details of how it works and most of the structures of the protein complexes involved are unknown. Two protein complexes have been identified as potentially defective in HD, and Mr. Rubinstein will be subjecting one of them (known as complex I) to exacting scrutiny.
Using the techniques of electron microscropy, he intends to formulate a three-dimensional structural model of complex I -- a model which could be important to the rational design of new therapeutic agents for Huntington disease.