Sherry AW

Drosophila Models of Neurodegenerative Disease

Profile

Sherry AW
Lab Location: #8-08   Email: syaw@imcb.a-star.edu.sg   Tel: 65869718

Sherry Aw obtained her BS in Biochemistry from the University of Wisconsin-Madison in 2003 and completed her doctoral studies at Harvard Medical School in 2009. During her postdoctoral training in Steve Cohen’s lab at the IMCB, she developed an interest in understanding the pathophysiology of neurodegenerative diseases. By carrying out a screen for microRNA mutants that exhibit defective motor function in the aging fly, she identified novel glioprotective and neuroprotective microRNAs. In addition, she led the development of a Spinach RNA-based microRNA sensor, Pandan, and a state-of-the-art optical fly tracking system. Sherry is a recipient of scholarships from the Economic Development Board and the Agency for Science, Technology and Research (A*STAR). She is a co-inventor on two patents, and was awarded the L'Oréal-UNESCO Singapore For Women in Science National Fellowship in Life Sciences 2017. She started her research group at IMCB in 2017.

Research

Drosophila Models of Neurodegenerative Disease

The lab takes a cross-disciplinary approach, combining genetics, biochemistry and chemistry, behavioural assays, high-speed imaging and computational analysis, to answer translational questions in neurodegenerative disease. To do this, we also collaborate closely with computer scientists, chemists and engineers to develop new tools and techniques for research and the clinic.

Molecular Mechanisms
We undertake functional screens to discover novel genes and mechanisms involved in the onset and progression of neurodegeneration.

Sherry Aw and Stephen Cohen (2012), Time is of the essence: microRNAs and age-associated neurodegeneration. Cell Research 22(8):1218-20
Sherry Shiying Aw*, Isaac Kok Hwee Lim, Melissa Xue Mei Tang, Stephen Michael Cohen* A glio-protective role of mir-263a by tuning sensitivity to glutamate. (Under revision) *Corresponding authors

Figure 1. Drosophila mir-263a serves a glio-protective role mediated by its regulation of glutamate receptor levels in astrocyte-like and ensheathing glia.

Cellular Context and Specificity

Many neurodegenerative diseases involve mutations in genes that are ubiquitously expressed; However, disease progression typically involves degeneration of select groups of cells, specific to each disease. We would like to understand the mechanistic basis of this selective degeneration. In addition, we are also interested in roles for glia in neurodegeneration

Figure 2. A subset of mir-263a-expressing glia (blue) in the Drosophila CNS, whose functions are linked to movement disorder. Dopaminergic neurons stained in red.


Technique development

We have a keen interest in developing new techniques that allow us to ask and answer novel questions.

- Pandan microRNA sensor
Aw, S.*, Tang, XM., Teo, YN*, Cohen, SM., (2016) “A conformation-induced fluorescence method for microRNA detection”. Nucleic Acids Research 2016 Jun 2; 44(10): e92. *Corresponding authors

MicroRNAs play important roles in many biological systems and show promise as clinical biomarkers. Innovation in techniques to sense and quantify microRNAs may aid research into novel aspects of microRNA biology and contribute to the development of diagnostics. By introducing an additional stem loop into the fluorescent RNA Spinach and altering its 3′ and 5′ ends, we generated a new RNA, Pandan, that functions as the basis for a microRNA sensor. We are further developing the sensor for genetic encoding in vivo, and as a clinical diagnostic tool.

Figure 3. Pandan is a bimolecular miRNA sensor. (A) Absence of the target miRNA prevents duplexes P3 and P4 from forming, hence destabilizing the G-quadruplex and base triplet required for proper folding and binding of DFHBI. (B) Pairing between miRNA and sensor backbone in stem-loops P3 and P4 allows for stable complex folding with DFHBI. The arrow indicates the second unpaired nucleotide 3′ of SL P3, 5′ of SL P4, that in all our tested sensors was a Uracil (U). The GGGA partial transcriptional start site is boxed. Based on Deigan-Warner et al.

- Optical tracking of fly movements
Fly models of neurodegeneration exhibit locomotor dysfunction. To better characterise these defects, we and our collaborators are developing an optical-based tracking system for fly movements.

Movement Disorders
Movement defects often accompany neurodegenerative diseases, and are used as a basis for diagnosis. We are using our optical tracking system to link cellular dysfunction to behavioral outputs, in order to understand the genes and circuits that underlie disease.

Staff

Department: Sherry AW

Name: Kangyu SU

Designation: Research Officer

Email: suky@imcb.a-star.edu.sg


Name: Mandy Yu Theng LIM

Designation: Research Fellow

Email: limytm@imcb.a-star.edu.sg


Name: Didem BARAN

Designation: SINGA Student

Email: didemb@student.imcb.a-star.edu.sg


Name: Asghar KHALILNEZHAD

Designation: Student

Email: asghark@student.imcb.a-star.edu.sg


Name: Kah Junn TAN

Designation: Research Officer

Email: kjtan@imcb.a-star.edu.sg


Name: Animesh BANERJEE

Designation: Research Fellow

Email: banerjeea@imcb.a-star.edu.sg


Name: Yi Li LIU

Designation: Asst Laboratory Officer

Email: ylliu@imcb.a-star.edu.sg


Publications

Sherry Shiying Aw*, Isaac Kok Hwee Lim, Melissa Xue Mei Tang, Stephen Michael Cohen*. (2017) ,
A glio-protective role of mir-263a by tuning sensitivity to glutamate.
Cell Reports,
19(9): 1783–93  
*Corresponding authors 22(8):1218-20

Aw, S.*, Tang, XM., Teo, YN*, Cohen, SM., (2016)
A conformation-induced fluorescence method for microRNA detection”.
Nucleic Acids Research
(March 6 2016) doi: 10.1093/nar/gkw108
*Corresponding authors.

Koe CT, Li S, Rossi F, Wong JJ, Wang Y, Zhang Z, Chen K, Aw SS, Richardson HE, Robson P, Sung WK, Yu F, Gonzalez C, Wang H. (2014)
The Brm-HDAC3-Erm repressor complex suppresses dedifferentiation in Drosophila type II neuroblast lineages
.
Elife
2014 Mar 11;3:e01906. doi: 10.7554/eLife.01906.

Li S, Wang C, Sandanaraj E, Aw SS, Koe CT, Wong JJ, Yu F, Ang BT, Tang C, Wang H. (2014)
The SCFSlimb E3 ligase complex regulates asymmetric division to inhibit neuroblast overgrowth.
EMBO Rep. 15(2):165-74

Sherry Aw and Stephen Cohen (2012)
Time is of the essence: microRNAs and age-associated neurodegeneration.
Cell Research
22(8):1218-20

Pai, V.*, Aw, S.*, Shomrat, T., Lemire, J., Levin, M. (2012)
Transmembrane Voltage Potential Controls Embryonic Eye Patterning in Xenopus laevis.
Development139(2):313-23
*Equal contribution

Aw, S., Koster, J., Pearson, W., Nichols, C. Shi, N.Q., Carneiro de Paula, K. and Levin, M. (2010)
The ATP-sensitive K(+)-channel (K(ATP)) controls early left-right patterning in Xenopus and chick embryos.

Developmental Biology, 1;346(1):39-53

Aw S. and Levin M, (2009)
Molecular mechanisms establishing consistent left–right asymmetry during vertebrate embryogenesis.

The Sinister Right Hemisphere: Cerebral lateralization and its possible role in psychosis, ed. Iris E. C. Sommer and René S. Khan. Published by Cambridge University Press

Sherry Aw and Michael Levin (2009)
Is left-right asymmetry a form of planar cell polarity?
Development
, 136:355-366

Sherry Aw and Michael Levin (2008), What’s Left in Asymmetry?
Developmental Dynamics, 237: 3453-3463

Aw, S., Adams, D. S., Qiu, D., and Levin, M., (2008),
H,K-ATPase protein localization and Kir4.1 function reveal concordance of 3 axes during early determination of left-right asymmetry.

Mechanisms of Development
, 125: 353-372