Catalyst Awardee

Project Description

Screening for therapeutic targets of NOTCH2NLC gene non-coding CGG repeat expansions associated neurodegeneration

Assistant Professor Zhou Zhi Dong, MD, PhD | National Neuroscience Institute (NNI); Professor Tan Eng King, MBBS, MRCP (United Kingdom), FAMS (Neurology), FRCP (Edinburgh) | National Neuroscience Institute (NNI)
Competition Sponsor: Ministry of Health and National Research Foundation of Singapore
Awardee year: 2022


Recently, pathogenic non-coding CGG repeat expansions in the neuroblastoma breakpoint family member 19/ notch 2 N-terminal like C (NOTCH2NLC) gene are found to the cause of Neuronal Intranuclear Inclusion Disease (NIID). Furthermore the non-coding CGG repeat expansions in the NOTCH2NLC gene can be the pathogenic factor of comprehensive neurodegenerative conditions, including dementia and Parkinsonism. However, the pathophysiological mechanism of non-coding CGG repeat expansion diseases remains to be elucidated. No therapeutic targets have been identified and no therapies have been developed. In our current study. we will perform high throughput single cell sequencing (SCS) of neurons from transgenic (Tg) NOTCH2NLC gene CGG expansion mice to search for therapeutic targets of non-coding CGG expansion associated neurodegeneration. SCS analysis of transcriptome (mRNA sequencing, scRNA-seq), translatome (ribosome profiling sequencing, scRibo-seq) and methylome (epigenetic sequencing, scMT-seq) will be performed. Potential therapeutic target identified from SCS study will be further validated in our NOTCH2NLC gene CGG expansion patient cells derived human neuron models. Our study aims to enhance clinical diagnosis, treatment and prognosis assessment of CGG expansion neurodegeneration and finally improve our life quality.

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