A Fly model for studying Amyotrophic Lateral Sclerosis

Current: Namrata Kulkarni, Lovleen Garg, Alex Varghese, Sanhita Sarkar, Vidyadheesh Kelkar

Past: Shweta Tendulkar,  Bhagyashree Kaduskar, Kriti Chaplot, Aparna Thulasidharan

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a late-onset, progressive disorder that culminates in the death of motor neurons of the brain cortex, brain stem and the spinal cord. This causes loss of signaling between motor neurons and voluntary muscles, causing paralysis and subsequent death of the patient. We study molecular and genetic aspects of the disease using the 8th ALS locus discovered in humans, the vesicle-associated membrane protein-associated protein B (VAPB) gene. A Proline to Serine mutation VAPB(P56S) causes ALS in humans and the same has been modeled in the fruitfly gene, VAPB(P58S). We use two models, one where VAPB(P58S) is expressed in neurons using the UAS-Gal4 system and the second where a null allele of VAPB is rescued by expression of transgenic VAPB. Our working hypothesis is that many, if not all of the ALS causative loci are connected by genetic interactions and the path to understanding initiation and progression of the disease leads from understanding the relationships between these loci. With this goal in mind we first defined a gene interaction network for VAPB in neurons (Deivasigamani  et. al., 2014) and followed this by studying the genetic interaction between ALS1/SOD1 and ALS8/VAPB (Chaplot et. al., 2019). Currently we are studying roles for the interesting relationship between TER94/AL14 and ALS8/VAPB (Tendulkar et. al, Manuscript in preparation)..