Investigating the Role of Sti1 in Preventing TDP-43 Misfolding in a Zebra Fish Model of ALS

ALS (amyotrophic lateral sclerosis) is an incurable neurodegenerative characterized by the dysfunction and then death of motor neurons due to misfolded proteins. While healthy cells are equipped with a defence mechanism against protein misfolding known as protein quality control, it is possible that some neurons in ALS lose this mechanism. It is unknown why TDP-43 misfolds in ALS, and why the protein quality control process is unable to prevent this. To investigate this, we will narrow our research in on chaperones such as Sti1, a key component of the protein control process. In a collaborative research initiative to decipher why Sti1 fails to prevent TDP-43 mis-folding in ALS motor neurons, we will use a zebra fish model of TDP-43 toxicity. This model is unique in that it allows us to investigate the Sti1-TDP-43 interaction in an organism holistically, through genetic, biochemical, cell biological, physiological, and behavioural approaches. Thus, we will be able to determine how Sti1 modulates TDP-43 in motor neurons and determine the effect on muscle function. This work will shed light on how specific molecular chaperones, in the protein quality control process, modulate protein misfolding. TBC

Faculty Supervisor:

Martin Duennwald

Student:

Partner:

ICM - Hôpital Pitié Salpêtrière

Discipline:

Life Sciences

Sector:

Education

University:

Western University

Program: