©2019 by sherryawlab.com

RESEARCH

If you have a passion for neurodegeneration research and are interested in

joining the lab, please email Sherry.

 

STUDY OF MOVEMENT DISORDERS USING MACHINE VISION

Movement defects often accompany neurodegenerative diseases, and are used as a basis for diagnosis. Fly models of neurodegeneration also exhibit locomotor dysfunction. To enable detailed behavioural phenotyping in fly disease models, we developed a machine-learning leg tracking method, Feature Learning-based Leg SegmentatIon and Tracking (FLLIT). Using FLLIT to analyse movement signatures of fly models of Parkinson's Disease (PD) and Spinocerebellar ataxia 3 (SCA3), we found that these models exhibit distinct gait signatures that resemble the respective human diseases. We are now using the system to link cellular dysfunction to behavioral outputs, in order to understand the genes and circuits that underlie disease. 


Reference:

Shuang Wu, Kah Junn Tan, Lakshmi Narasimhan Govindarajan, James Charles Stewart, Lin Gu, Joses Wei Hao Ho, Malvika Katarya, Boon Hui Wong, Eng King Tan, Daiqin Li, Adam Claridge-Chang, Camilo Libedinsky, Li Cheng* and Sherry Shiying Aw*# 

Fully automated leg tracking of Drosophila neurodegeneration models reveals distinct conserved movement signatures. 

PLOS Biology (2019) 17(6) (View)

*Corresponding authors     #Lead contact

 

MOLECULAR AND CIRCUIT MECHANISMS UNDERLYING MOVEMENT DISORDERS

Using FLLIT, we can now use quantitative phenotyping to characterise genes and neuronal populations whose dysregulation underlie movement disorders.


I) Tremor

Essential Tremor (ET) is the most common movement disorder, with a high familial risk. The rare risk variants that have been identified account for a small fraction of disease risk, indicating that key causative genes remain to be discovered. We have identified a neuronal population whose function is required to prevent tremor in the fly, and are working to understand their normal function and dysregulation in disease.


II) MicroRNAs and movement disorders

One class of genes that we are interested in are microRNAs, and the targets that they regulate to protect against movement disorder.

References:
Aw, S. *#, Lim, KH, Tang, XM, Cohen, SM* (2017) 

A glio-protective role of mir-263a by tuning sensitivity to glutamate. 

Cell Reports 19(9): 1783–93
*Corresponding authors           #Lead contact

Sherry Aw and Stephen Cohen (2012). Time is of the essence: microRNAs and age-associated neurodegeneration. 

Cell Research 22(8):1218-20

 

DEVELOPMENT OF MICRORNA SENSORS

We are further developing our sequence-specific, Spinach RNA-based microRNA sensor, Pandan, for use as a research tool in vivo, and as a diagnostic tool for use in the clinic.

Reference:
Aw, S.*#, Tang, XM., Teo, YN*, Cohen, SM. (2016) 

A conformation-induced fluorescence method for microRNA detection.
​Nucleic Acids Research 44 (10): e92, doi: 10.1093/nar/gkw108
*Corresponding authors.    #Lead contact

 

ROLE OF GLIA IN NEURODEGENERATION

Glia play important neuroprotective roles. We use a functional approach to understand how glial dysfunction can contribute to neurodegeneration.

Reference:
Aw, S. *#, Lim, KH, Tang, XM, Cohen, SM* (2017) 

A glio-protective role of mir-263a by tuning sensitivity to glutamate. 

Cell Reports 19(9): 1783–93
*Corresponding authors           #Lead contact

 

FUNDING