Brain growth and disease


Current research projects - NOW HIRING POSTDOCS AND PhD STUDENTS
Associate Professor Julian Heng studies the molecular and cellular mechanisms which control fetal brain development, with particular emphasis on the production of new nerve cells and their development as functional circuits. This research has significant implications for the diagnosis and treatment of brain disorders. In addition, our discoveries contribute to the development of future therapies which enhance the limited regenerative capacity of the adult brain to repair itself through the formation of appropriate replacement circuits in times of injury or stress.

The following projects are available within the lab:

(left) Fetal mouse brain cells labelled with green fluorescent protein (GFP)
expression to study their development. (right) Confocal microscopy image
of a section of mouse brain tissue which identifies GFP-labelled cells and
Ctip2-expressing cells. © Julian Heng






Project 1) Do mutations to the gene regulatory protein RP58 cause brain disorders in children? 

Recent improvements in genome sequencing technologies have empowered researchers and clinicians with a means to investigate the genetic basis for neurological disorders that result from copy-number variation (CNV). However, what continues to remain a challenge is to establish the pathogenicity of genomic abnormalities, such as CNVs, and their causative effects on nervous system impairment. In this project, we clarify possible genotype-phenotype relationships in human subjects with brain developmental disorder which are associated with microdeletions to 1q43-44. Our investigation has led to the identification of ZNF238 as a critical gene for brain development. Using a range of molecular and cellular approaches combined with in utero electroporation with mice, the goal of this project is to understand how loss of ZNF238 leads to impairments in the production of cerebral cortical neurons during fetal development. This work leads to an improved understanding of the molecular basis for 1q43-44 CNVs in human health and mental dysfunction.

 

Project 2) Harnessing Human Genetics to Discover Novel Molecular Pathways for Neuronal Development 

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.

 

Project 3) Understanding the cellular and molecular basis for neuronal migration during brain development and disease 

Migration is a universal property of all newborn neurons of the developing mammalian nervous system (Heng et al, 2010, TiNS). 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.

 

Please contact Julian Heng for details.

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