Brain growth and disease


Student project opportunities

Do mutations to the gene regulatory protein RP58 cause brain disorders in children?

Research area: Molecular Biology, Developmental Neurobiology, Stem Cell Biology, Control of brain growth
Chief supervisor: Associate Professor Julian Heng
Project suitable for: Honours, Masters or PhD  
Essential qualifications: BSc 
Start date: Flexible

Project outline
The growth of the fetal brain involves many steps, including the production of new nerve cells, their proper placement within this growing organ, and the establishment of functional connections to other brain cells (reviewed in Heng et al, 2010; Harris et al, 2016).  The molecular control of these steps relies on the functions of DNA-binding gene regulatory proteins such as RP58 (Heng et al, 2013; Ohtaka-Maruyama et al, 2013). Recently, we reported that mutations to RP58 underlie human brain disorder (Hemming et al, 2016). In this project, we will ask how disease-associated mutations to RP58 influence neuronal development within the mammalian fetal brain.  This biological question will be tackled using animal models as well as cell culture techniques to:
(i) catalogue the changes in gene expression as a result of RP58 gene disruption
(ii) define the role for RP58 in the development of cerebral cortical neurons
(iii) develop a model to understand how mutations to RP58 might disrupt the development and connectivity of human neurons.

References

  1. Harris L et al. Stem Cells International. 2016. doi: 10.1155/2016/9745315
  2. Hemming IA et al. American Journal of Medical Genetics Part B Neuropsychiatric Genetics. 2016 Feb 7. doi: 10.1002/ajmg.b.32427
  3. Heng JI et al. 2010 Trends in Neurosciences, 2016, 33(1):38-47
  4. Heng JI et al. Cerebral Cortex. 2013. doi: 10.1093/cercor/bht277. Epub 2013 Oct 1
  5. Ohtaka-Maruyama et al. Cell Reports. 2013 Feb 21;3(3):458-71. doi:10.1016/j.celrep.2013.01.012

Contact
Julian Heng - julian.heng@perkins.uwa.edu.au

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Understanding the cellular and molecular basis for neuronal migration during brain development and disease

Research area: Molecular Biology, Developmental Neurobiology, Confocal Imaging Microscopy
Chief supervisor: Associate Professor Julian Heng
Project suitable for: Honours, Masters or PhD 
Essential qualifications BSc
Start date: Flexible

Project outline
Migration is a universal property of all newborn neurons of the developing mammalian nervous system (Heng et al, 2010; Harris et al, 2016). In this project, we will study the functions for protein-coding genes which regulate the ability for immature neurons of the cerebral cortex to position themselves appropriately within the growing fetal brain. We will apply these findings to understand the genetic basis for neuronal migration disorders in humans. This area of work has significant implications for the enruobiology of early onset mental health conditions such as autism spectrum disorder, psychosis and epilepsy (Gladwyn-NG et al, 2016; Sim et al, 2016)

References

Gladwyn-Ng et al. Neural Development. 2016, 11:7 doi: 10.1186/s13064-016-0062-1
Sim J et al. Annals of Neurology. 2016 Jan;79(1):132-7. doi: 10.1002/ana.24502

Contact
Julian Heng -  julian.heng@perkins.uwa.edu.au

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Harnessing Human Genetics to Discover Novel Molecular Pathways for Neuronal Development


Research area: Molecular Biology, Developmental Neurobiology, Confocal Imaging Microscopy
Chief supervisor: Associate Professor Julian Heng
Project suitable for: Honours, Masters or PhD
Essential qualifications BSc
Start date: Flexible

Project outline
During fetal development, the growth of the cerebral cortex relies on a step-wise process of neurogenesis, cell migration and circuit formation. Failures in these key developmental steps can result in brain disorder and lead to intellectual disability. The goal of this project is to study the neurobiology of brain development disorders with a genetic origin, as well as to characterise novel players in brain development and disease. Through this research, we will better understand the molecular and cellular functions within the developing brain which guide the development of new neural circuits as they fire and wire appropriately. We will apply this knowledge towards developing tools which improve the genetic diagnosis and clinical management of patients born with brain disorders such as epilepsy, intellectual disability and autism (Breuss et al, 2012; Haas et al, 2016).

References

Haas et al. Cell Reports. 2016 Jun 7:15(10):2251-65. doi:10.1016/j.celrep.2016.04.090
Breuss M et al. Cell Reports. 2012 Dec 27:2(6):1552-62 

Contact
Julian Heng -  julian.heng@perkins.uwa.edu.au

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