My research group is interested in deciphering the genetic components that regulate the molecular networks underlying the development of the mammalian brain (please visit the group site for more information). Our current research focus includes: (1) characterisation of the role of long non-coding RNAs during brain development, (2) characterisation of novel microRNAs involved in embryogenesis (3) transcriptomic analysis of Down syndrome mouse brain, and (4) molecular screening of nucleic acid aberrations in selected neurological disorders.
Distorted communications between proteins have been proposed as the cause of various mental health conditions including mental disability of various spectrum especially in patients diagnosed with autism, schizophrenia, Down syndrome or Alzheimer’s disease. Unfortunately, our current understanding on the communicational networks between proteins during normal brain development remains inadequate.
Since the mouse and human share about 85% of imprinted information and undergo almost identical brain developmental stages, we, therefore, in collaboration with Professor Hamish Scott (University of Adelaide), studied the mouse brain obtained from various developmental stages that resemble the human brain at the first trimester, third trimester, after birth as well as at senescence. In the analysis we compared and noted all the changes of the amount as well as type of mRNAs found in each stages of brain development and use them to infer the underlying communicational networks at the protein level. From our observations, we outline a benchmark for networks comparison between the normal and abnormal brain development conditions. We identified 70 mRNAs/proteins and groups of novel RNAs that do not bear any information for the production of proteins. These mRNAs or novel RNAs were specifically produced in specific regions of the brain at specific developmental stages. Our group are interested in deciphering the role of these differentially regulated transcripts in brain development.
Figure 1: An example of how molecules are connected intracellularly (A) and related to various neurological disorders (B). Sourced from Ling et al, Genome Biol, 2009; 10(10):R104.
Figure 2: The expression profile of a novel non-protein coding transcript known as Nrgn antisense transcript in different adult mouse brain cells. Sourced from Ling et al, Cereb Cortex, 2010: doi:10.1093/cercor/bhq141
Project Title Funding Source The association of CDKL5 and STXBP1 gene mutations in paediatric patients with early-onset epileptic encephalopathy in Malaysia Geran Putra IPS, UPM Expression profiling of a novel microRNA, miR-3099, during neuronal development using an in vitro system RUGS, UPM A mouse embryonic stem cell culture system with stable and regulatable expression for a novel microRNA, miR3099: An in vitro approach towards functional genomic study. FRGS, MOE Identification of molecular mechanism responsible for hypotonia in adult Ts1Cje mouse model of Down syndrome RUGS, UPM
[publication publisher=”Michael KH Ling”][/publication]
Year Name of Award 2006 Excellence Service Award by UPM 2009 Best Poster Presentation Award by Australian Society for Medical Research 2009 Discipline of Medicine Traveling Fund, University of Adelaide 2009 FHS Postgraduate Traveling Fellowship Award, University of Adelaide 2012 CCB PhD Thesis Research Excellence Award, Centre for Cancer Biology, Adelaide, Australia 2011 Dean of Graduate Studies Special Commendation on Outstanding PhD Thesis Award, University of Adelaide 2012 Best Poster Presentation in conjunction with 4th MTERMS, Langkawi, Malaysia 2011 Lindau Foundation Young Scientist Fellowships 2012 IBRO-SfN Travel Grant
Current Lab Members
Name Position Research Interest Year Joined Asween Rowena Binti Abdullah Sani PhD student Screening and functional characterisation of genetic polymorphisms among subjects diagnosed with Major Depressive Disorder (MDD) 2014 Han Chung Lee PhD Student In utero characterization of neurogenesis in Ts1Cje mouse model for Down syndrome 2013 Pui Yee Melody Leong Masters Student Transcriptomic Analysis of Skeletal Muscles Isolated from Ts1Cje Mouse Model for Down Syndrome 2014 Shahidee Zainal Abidin Scientist 2014
Michael KH Ling