Gene Network Disruptions and Neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome.
by Michael KH Ling Comments are off
About the Author
Michael KH Ling
My research group is interested in deciphering the genetic components that regulate the molecular networks underlying the development of the mammalian brain. 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