This summer two HOPES team members, Taylor Altman and Shawn Fu, spent several days with Drs. James Gusella and Marcy MacDonald at their laboratories in the Molecular Neurogenetics Unit of Massachusetts General Hospital (MGH) in the Boston area. HOPES would like to thank Gusella and MacDonald for taking the time to share many valuable insights with us.
The Molecular Neurogenetics Unit, under the direction of Gusella, is dedicated to using molecular genetic techniques in humans and mice to understand and treat neurological disorders. Gusella and his colleagues pioneered the use of DNA sequence polymorphisms as genetic markers and mapped the Huntington gene to chromosome 4 in 1983 (please click here for more information about this breakthrough). He and his fellow researchers have since applied this genetic mapping approach to numerous neurological diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Batten disease, and familial dysautonomia (FD) in an effort to pinpoint the chromosomal locations of the disease genes and/or the nature of the genetic defect itself. In 1993, Gusella, MacDonald, and their colleagues, as part of an international collaboration, identified an expanded, unstable CAG trinucleotide repeat in a novel gene as the cause of Huntington’s disease.
Both Gusella and MacDonald are currently trying to understand the pathogenesis of HD and find ways to interfere with the disease cascade in order to halt its progression. According to the webpage of the MacDonald laboratory, she and her colleagues follow three interrelated steps in order to investigate the complex biology behind HD and other neurological disorders:
The use of polymorphic DNA markers in genetic family studies to isolate gene defects that cause inherited disorders of the nervous system and test loci that alter the disease phenotype in some way.
The creation of model systems (such as the mouse model of HD) in order to understand and clarify the functions of the products (essentially, proteins) of the abnormal gene at the whole animal, cellular, and biochemical levels.
The use of model systems to explore novel gene therapy based strategies, which aim to intervene in the disease process.
MacDonald uses knock-in mice that carry human mutations, such as the gene defects in HD and Batten disease, to identify early cellular and molecular events in the disease pathways. She is also in the process of identifying cellular partners (the parts of the cell that a chemical or molecule interacts with) and pathways for the HD and Batten disease proteins, huntingtin and battenin.
The MacDonald lab
Last Modified: 05/22/2009
An educational product of HOPES, not to be used in place of medical care. For more information about HOPES, click on the Logo.
To contact HOPES with comments or questions, click here.
