In 2019, a team of scientists led by co-recipient Dr. Sali Farhan discovered a new genetic cause of ALS called DNAJC7. Subsequent work revealed that mutations in the DNAJC7 gene lead to production of a protein that is unable to perform its normal function in cells. However, it is not yet known exactly how this impaired protein contributes to the development of ALS. For this project, yeast and protein folding expert Dr. Martin Duennwald will collaborate with Dr. Farhan to better understand the role of DNAJC7 in causing ALS.
It has been previously established that the DNAJC7 protein is part of a system called the heat shock response, which helps to guide the proper folding (e.g., shape) of other proteins within cells. Here, the team will focus their efforts on understanding if the loss of DNAJC7 function affects the folding of two other prominent ALS-causing proteins, TDP-43 and FUS. These proteins are known to become misfolded in ALS and are thought to play a role in the ensuing neurodegeneration.
The team will also gather clinical information from people with DNAJC7 mutations in order to better understand the clinical characteristics of this form of the disease. In a collaborative study, led by Dr. Kevin Eggan at Harvard University, the team will analyze motor neurons and other cell types derived from these individuals.
By gaining a better understanding of the biological pathways affected by DNAJC7 mutation and the subsequent loss of function, these scientists will hopefully be able to pinpoint new targets and strategies for the treatment of ALS.