Investigator:
Satya Surabhi, PhD
Name of Institution:
Albert Einstein College of Medicine, Bronx, NY
Project Title:
The role of Lamp1 in age-related neurodegenerative diseases
Investigator Bio:
Dr. Surabhi is an Associate in Prof. Andreas Jenny’s lab in the Department of Developmental and Molecular Biology at the Albert Einstein College of Medicine, New York, NY. Her research interests involve the development of a comprehensive understanding of key autophagy pathways and how alterations in these pathways can contribute to human neurodegenerative diseases like Parkinson disease (PD), using a Drosophila or fruit fly model. She has a particular interest in the role of lysosome-associated membrane protein 1 (Lamp1) in age-related neurodegenerative diseases. Dr. Surabhi’s recent findings reveal a novel role for Drosophila Lamp1 in neuronal protection against oxidative stress and neurotoxicity in PD models. Dr. Surabhi completed her Ph.D. under the supervision of Prof. Mousumi Mutsuddi in the Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India. After obtaining her Ph.D. degree, she moved to Evanston, IL, to join the lab of Prof. Ravi Allada as a postdoctoral fellow in the Department of Neurobiology at Northwestern University and worked on the mechanism of temperature adaptation of the circadian rhythm in fruit flies.
Objective:
Using fruit flies as a model system, we aim to understand the mechanism by which Drosophila Lamp1 affects a-synuclein clearance in the brain.
Background:
PD destroys certain neurons in the brain due to the failure to remove a protein called a-synuclein. It is important to understand why the cellular protein degradation machinery sometimes cannot cope with a-synuclein. In a cell, lysosomes are acidic organelles that degrade many proteins. Critical for this process are members of the lysosome associated membrane protein (LAMP) family. Intriguingly, the consequences of defective Lamp1 resemble the loss of Glucocerebrosidase 1 (GBA1), a major genetic risk factor for PD.
Methods/Design:
In a commonly used fly model of PD in which human a-synuclein is expressed, many disease characteristics, including motion issues, are faithfully represented. We will use this fly model to determine how Lamp1 affects the solubility and aggregation of a-synA30P, a disease associated from of a-synuclein, and of other markers relevant for protein degradation including the autophagy adapter protein p62, and ubiquitin. We will assess if mutation of Lamp1 changes a-synuclein localization or its environment in degradative acidic endo-lysosomes. Additionally, due to the similarity of the Lamp1 and Gba1 mutant phenotypes, we will test whether Gba1 and Lamp1 affect each other. We will assess protein co-localization of Lamp1 and Gba1b. We will also determine the effects of each mutation on the other and on a variety of components of the endo-lysosomal protein degradation system.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Overall, this work will use the fruit fly model to shed important light on the mechanisms by which PD develops.