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Automated Nematode Screening for Neurodegenerative Diseases

Automated Nematode Screening for Neurodegenerative Diseases 2020-2022
Acronym: ANS-ND
Budget: 600,000 RON
Project director: Robi Tacutu

The project aims to experimentally develop an integrated and automated solution for screening drugs and genetic interventions for neurodegenerative diseases, using the nematode C. elegans and ageing-related data.

Abstract:

Ageing is the major risk factor for neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. The graying of the population has been accompanied by a continual increase in the prevalence of neurodegeneration amongst the elderly and is now one of the greatest challenges that healthcare and research has to tackle. In this project, we propose to experimentally develop an integrated and automated solution for screening drugs and genetic interventions for neurodegenerative diseases, using the nematode C. elegans and ageing-related data. The system will include: 1) a network-based, integrative and predictive bioinformatics method for short-listing genetic targets of interest, and 2) a low-cost, modular, automated video-recording platform for healthspan screening in worms. Additionally, we also propose the implementation of a gene activation system that would complement the existing genetic tools for investigating gene function and drug screening in worms, by creating a CRISPR-based overexpression system with the flexibility of RNA interference approaches. Lastly, we propose to validate the developed system by monitoring predicted interventions, both using the automated platform and by traditional lab methods.

Project objectives:

The overall goal of the project is to build an automated system for phenotypic screening in nematodes which will be used to test predicted targets for neurodegenerative diseases. More specifically, the objectives are: 1) Predicting using a systems biology approach molecular targets relevant to ageing and neurodegeneration; 2) Building a low-cost, modular, video-monitoring system for nematodes, capable of simultaneously assaying lifespan and healthspan features for a large number of plates with worm cultures; 3) Expanding the current capacity of molecular interventions in worms with a method that allows the overexpression of specific targets, controlled through food-delivered dCAS9 CRISPR guides; and 4) Testing and validating the developed system by monitoring predicted interventions and comparing with traditional lab methods (manually culturing worms and observing their phenotype).

Estimated outcomes:

Upon the implementation of the project, the following outcomes should be achieved: 1) the group will have a functional prototype system (at the experimental proof of concept level) that allows with minimal human interventions to survey the lifespan and healthspan of multiple worm culture plates; 2) the group will have a validated protocol to overexpress genes in C. elegans using CRISPR; 3) the group will have evaluated phenotype changes for several interventions in relation to neurodegeneration.

Robi Tacutu, Ph.D.
Robi Tacutu, Ph.D.

Group leader

A thorough, analytical and curiosity-driven scientist, with a multidisciplinary background in biology and computer science, Robi received his BSc in computer science from the University Politehnica Bucharest, and his MSc in biochemistry and molecular biology from the University of Bucharest. He has a long-term commitment and interest in the field of biogerontology (since 2005) and received his PhD in 2013 from the Ben-Gurion University of the Negev, in the lab of Prof. Vadim Fraifeld. His thesis was on an ageing-related topic: studying the relationships between aging and age-related diseases with the use of bioinformatics and network biology approaches, and More...

Dmitri Toren
Dmitri Toren

Assistant researcher

Dmitri is a bioinformatics researcher at the Institute of Biochemistry, focusing on curation for aging-related data, analysis of large screen datasets, dataset annotation and network-based analyses. He is also a Ph.D. cand More...

Ioan Valentin Matei, M.D., Ph.D.
Ioan Valentin Matei, M.D., Ph.D.

Assistant Researcher

Ioan has a background in regenerative medicine, cell therapies, stem cell science and diabetes research. He has worked extensively on endocrine pancreatic cell differentiation, starting with his Ph.D. at the Nippon Dental More...

Simona Ghenea, Dr.
Simona Ghenea, Dr.

Researcher

Simona Ghenea is a researcher in the Institute of Biochemistry of the Romanian Academy. Simona is currently working in Molecular Cell Biology in the Molecular Cell Biology.