Investigating the role of TDP-43 in DNA Replication: Implications for ALS Pathogenesis
Aperçu du projet
Cells are constantly under stress due to several environmental and internal factors. Accumulating stress over a period as seen in aging and neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) puts additional pressure on the cell’s coping machinery. In ALS, neurons and glial cells exhibit altered cellular processes and many proteins fail to perform their normal function. In brain and spinal cord tissue samples collected from ALS patients, aggregation of TDP-43 protein is commonly observed. What causes the aggregation and how this influences the loss of TDP-43 function is still not clear. Our experimental evidence using proximity dependent labelling technique and high-resolution imaging shows that TDP-43 interacts with multiple proteins involved in the DNA replication process which suggests that TDP-43 could possibly play a critical role in replication process. The replication process is highly regulated, which is necessary for genome stability. We will investigate when and where TDP-43 is involved in replication and what is the function of TDP-43 in this process. Next, we will study how the different stress and mutations affect these functions in neurons and non-neuronal cells like astrocytes and their relevance to ALS disease mechanisms. This study will help us to understand the role of TDP-43 in genome stability. Also, this study will reveal how TDP-43 carries out important tasks to help cells cope with stress conditions which will ultimately aid in the development of therapies to improve the lives of patients affected by ALS.
Chef d'équipe
Sahana Talanjeri Gopalakrishna , University of Toronto
Partenaire et Donateurs
Allan Kliger, Aviva Rajsky & Family