HSCI RESEARCH SEMINAR SERIES SCHOOL OF HEALTH SCIENCES

HSCI696 will be presented synchronously through simulcast. The link below can be used for the live stream. Authentication is not required. RHPH 172 Live Stream

“Development of sorl1 knockout zebrafish model using CRISPR/Cas technology to understand sporadic Alzheimer's Disease”

Arjun Pitchai PhD candidate and visiting PhD student from Sathyabama Institute of Science and Technology in Chennai, India. Host: Jennifer Freeman

Tuesday, September 8, 2020 RHPH 172 4:30-5:30 PM

Abstract: Alzheimer’s Disease (AD), the most prevalent human neurodegenerative disease, represents a grow ing burden to our public health. There are tw o broad classes of AD (i) the Familial Alzheimer’s Disease (FAD), characterized by genetic mutations in specific and manifests early in life and (ii) the prevalent sporadic form (developing at age > 65).The hallmark symptoms of both AD forms includes increased levels of Amyloid-β (Aβ)1−42 aggregated in senile plaques and tangles of hyperphosphorylated tau. Sporadic AD accounts for more than 95% of all AD cases and is linked to the ε4 (APOE) allele and Sortilin-related receptor (SORL1). SORL1 is a genetic risk factor for sporadic AD. It has been show n that amyloid precursor (APP) can be diverted aw ay from the late endosomal pathw ay by a SORL1-dependent sw itch, w hich sequesters APP into recycling endosomes, preventing the formation of Aβ. Reduced expression of SORL1 is seen in AD brain tissue and is associated w ith an increase in Aβ production. Using the genome-engineering technology called clustered regularly interspaced short palindromic repeats (CRISPR), a zebrafish model w ith reduced expression of sorl1 is being developed to understand amyloid plaque formation and inhibition. The zebrafish has numerous strengths as a laboratory test model for various human diseases. This model has a finished genome sequence and shares high genetic similarity w ith humans. Moreover, there are several zebrafish orthologs related to human neurodegenerative diseases including AD, enabling the application of this fish model for the study of AD. Of potential benefit in the elucidation of a link betw een sorl1 and AD, a gene coding for a sorl1-like protein is located on zebrafish 15. In zebrafish, the CRISPR/ Cas system can generate gene knockouts w ith very high frequency (75-99%). The inhibition study w ill be initiated by using the administration of neuroactive molecules into the KO model. In the presentation, the concept and methods for developing sorl1 gene knockout and its applications w ill be discussed.