C. elegans Model of Neurodegeneration, Mitochondrial Dysfunction, and Aging

TOPICAL COLLECTIONS

C. elegans Model of Neurodegeneration, Mitochondrial Dysfunction, and Aging

Guest Editor

Sanjib Guha

University of Rochester Medical Center

Dr. Guha was born and raised in Calcutta, India where he did his undergrad studies. Then in 2008, he moved to California where he completed his Masters in Biological Sciences from California State University, East Bay. After that he moved to Singapore, where he worked as a research associate at National University of Singapore. Then he moved to Barcelona (2011), where he did his PhD on Neuroscience from Pompeu Fabra University and after that he returned back to California, where his first postdoc was at the Buck Institute with Prof. Kapahi (2016) on aging and neurodegenerative diseases. After that, he moved to Rochester, Upstate New York to continue his postdoctoral studies by working at the labs of Prof. Keith Nehrke and Gail Johnson (2019). Recently, he has been promoted as a staff scientist at his department of Anesthesiology, and continue working on his project where he is trying to find out how post-translational modifications of tau selectively impact neurodegeneration and causes mitochondrial dysfunction. The initial observational study is published at Molecular Neurodegeneration and the corresponding review article he published at Molecular Neurobiology (2020). As a globe trotter, he did his higher studies from 3 different countries, lived in 7 different cities and can speak 5 languages. Also, he is a pioneer mentor at an organization called Freedom Employability Academy, where he helps the under-privileged students better understand what professional paths are available to them, which of those might be appropriate to them, and what they need to do to get there.

Collection Overview

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with pathological hallmarks including intraneuronal neurofibrillary tangles (NFTs) composed of the microtubule-associated protein Tau and accumulation of extra-cellular amyloid plaques made up of amyloid-β protein. Parkinson’s disease (PD) has the neuropathological hallmark of the loss of dopaminergic neurons from the substantia nigra associated with the presence of intraneuronal inclusions called Lewy bodies. In addition, mitochondrial dysfunction is an early feature of these major neurological disorders. A major bottleneck in understanding the mechanisms behind the neurotoxicity is the lack of genetically tractable models that can recapitulate the effects of toxic aggregated proteins in a short time frame. With its simple anatomy and short life cycle, the C. elegans model perfectly fills this gap. It is an excellent tool for doing genetic analysis and has a transparent body which helps in visualizing any fluorescent proteins or biosensors live in vivo. And lastly, it is an ideal model to screen for small therapeutic compounds to see an effect on aging or neuronal damages.

This Methods Collection includes C. elegans model to mimic pathological hallmarks of major neurodegenerative diseases. Since mitochondria is a known key player with impact on neuronal structures, this Methods Collection also includes well-described fluorescent biosensors designed to reflect changes in various aspects of mitochondrial physiology to establish metrics of neuronal dysfunction during aging. These sensors include mito-roGFP1 (redox status), A-Team2.0 (ATP), mitoHyper (H₂O₂), and mitoTimer (mitochondrial lifetime/turnover). Lastly, this Collection includes any drug screening platform that can improve neuronal integrity and simultaneously boost mitochondria health.