Neuroscience is one of the escalating and most fascinating endeavours of biology research today. Neuroscience research has advanced knowledge on how a brain functions, how a neurone behaves and how damaged neuronal networks may lead to various neurological disorders. In Universiti Putra Malaysia (UPM), neuroscience research is now one of the priority niche areas. Besides, steps have been taken to gather both the scientists and clinicians who venture in the field by pooling resources and practicing knowledge sharing. Our research group, known as NeuroBiology and Genetics Group (NBGG), is interested in unraveling the role of genetic factors and molecular networks that regulate the development and function of the mammalian brain. Our group place a great emphasis in three main areas of research; (1) neurological disorders, (2) non-coding RNA roles in brain development and function and (3) technology transfer and development on gene delivery platform.
NBGG is involved in deciphering the genetic landscape leading to disrupted molecular pathways and processes responsible for Down syndrome pathology (trisomy 21) and associated disorders (defective neurogenesis and intellectual disability). With limited access to Down syndrome patient tissues and the lack of comprehensive investigations at the molecular level, we have employed Ts1Cje, a mouse model for Down syndrome to facilitate genetic dissection of the learning, behavioural and neurological abnormalities in Down syndrome. In collaboration with Professor Hamish Scott from the University of Adelaide, South Australia, we profile gene expression pattern at various regions of the Down syndrome brain at different stages of development. Spatiotemporal comparisons of gene expression profiles between the normal and Down syndrome brains provide a great genetic overview that may provide clues on what has gone wrong in the Down syndrome brain. In addition to the brain development, our interest also extends to identifying the molecular mechanism responsible for hypotonia (decrease in muscle tone), a cardinal feature, in Down syndrome. Our group plans to generate a comprehensive catalogue of molecular and cellular properties that affect locomotor functions and vesicle recycling mechanism at the neuromuscular junction of the Ts1cje mouse model. The ultimate aim of our research is to determine the effect of the additional gene dosage in the trisomic model. In the long term, NBGG aims to develop molecular therapies that may improve the quality of life among Down syndrome patients.
A different branch of NBGG research is to understand the role of non-coding RNAs in regulating the development of the mammalian brain. Our group has a special interest in characterising the molecular role of a few novel microRNAs (miRNAs), that are found to be expressed throughout embryonic development especially in the brain. miRNAs are short RNA sequences with 18-24nt in length. miRNAs target mainly at the 3’ UTR of mRNA to either repress translation processes or promote mRNA degradation. In both cases, miRNAs will influence the level of protein synthesis. When the phenomenon happens at a global scale, changes of the amount of proteins synthesised may affect the phenotypic characteristics of the cell. In the context of a developing brain, miRNAs may play a crucial role in regulating neurogenesis, neuronal differentiation and function. To dissect the molecular role of these novel miRNAs, NBGG plans to use various techniques such as in situ hybridisation, stemloop-RT-qPCR, overexpression studies, Western blotting and luciferase assay analysis in various models such as mouse embryonic stem cells, differentiated neurones, primary neuronal cultures and brain sections.
To complement our efforts in elucidating the role of various candidate genes and miRNAs in brain development or function, our group is in the midst of establishing a “super electroporator” platform for the delivery of charged particles into specific regions of the mouse brain. Charged particles such as DNA constructs with Green Fluorescent Protein (GFP) as traceable gene reporter system have been established in our laboratory and are ready to be electroporated into the developing mouse brain in utero. The platform will facilitate us to trace the formation of defective migratory routes of neurones in the Down syndrome brain in the presence or absence of selected candidate trisomic genes. The platform also enables us to study the function of novel miRNAs in a spatiotemporal manner throughout the development and maturation of the brain.
Our group also works with clinicians to screen for aberrations of selected genes in Parkinson’s disease and infantile spastic patients. In addition, we look forward to any queries regarding our research projects and welcome any potential collaborators to work on the following extended research topics:
a) Advancement of the ‘super electroporator’ platform and its applications in in utero, in vitro as well as in vivo delivery of charged particles.
b) Identification and characterisation of natural products that may improve the learning and memory capability in Ts1Cje mouse model.
c) Exploration of the role of novel miRNAs in early embryo development.
d) Characterisation of candidate noncoding RNAs in human Down syndrome induced pluripotent stem cell (iPSC)-derived neurones.
e) Elucidation of long noncoding RNAs roles in gene expression regulation in the mammalian brain via bioinformatics and genomics approaches.
Dr. Michael KH Ling:
[email protected] +603-89472564
Dr Ling’s Scientific Malaysian profile: http://www.scientificmalaysian.com/scimy/members/michaelling/
Dr. Pike-See Cheah:
[email protected] +603-89472355
Dr Cheah’s Scientific Malaysian profile: http://www.scientificmalaysian.com/scimy/members/pikesee/
Research Cluster: http://medic1.upm.edu.my/jog/neuro/