Epigenetics and Genomics


Student project opportunities



Identifying the regulatory factors associated with neuronal maturation in vivo

Research area: Genomics, gene regulation, brain development
Chief supervisor: Professor Ryan Lister
Project suitable for: Masters or PhD
Essential qualifications: BSc
Start date: Flexible

Project outline 

While pluripotent stem cells (PSCs) offer great potential for the derivation of mature cell types for therpeutic use and disease modelling, it is now known that cell types generated from PSCs resemble immature fetal-like cells. The functional immaturity of PSC-derived lineages poses serious challenges to their utility in clinical, drug screening and research contexts. For example, neurons differentiated in vitro only progress to a developmental stage that resembles fetal neurons, precluding the accurate modelling and investigation of neural disorders that occur in adulthood in functionally and molecularly mature aged neurons (e.g Alzheimer’s, Parkinson’s). PSC differentiation into specialized cell types in vitro is known to mimic in vivo developmental processes, thus this project will perform comprehensive characterization of the transcriptional regulatory landscape and gene expression changes in neuronal subtypes of the frontal cortex throughout brain development from gestation to adulthood in humans and mice. Understanding how these developmental pathways are regulated in vivo is foundational for identifying how to rapidly, efficiently and artificially impose the cellular states of mature cells onto immature progenitors in vitro.


Contact
Professor Ryan Lister - ryan.lister@uwa.edu.au 

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Computational reconstruction of chromatin structure from DNA methylation profiles

Research area:  Genomics, bioinformatics, computational biology
Chief supervisor: Professor Ryan Lister
Project suitable for: Honours, Masters, or PhD
Essential qualifications: BSc
Start date: Flexible

Project outline

Mammalian genomes contain tens of millions of cytosine bases that have been modified to form methylcytosine, which in some instances can regulate local transcriptional activity. It has been observed that when proteins, such as transcription factors, bind to DNA, the local chromatin state is altered and methylcytosines within the vicinity can become demethylated. Consequently, the millions of methylcytosines throughout the genome may be considered as individual sensors for local protein binding activity. Comphrehensive maps of DNA methylation state throughout the genome, which can now be routinely generated with existing high throughput DNA sequencing technologies, thus constitute an information rich datatype from which protein binding activity could potentially be detected from DNA alone. This would provide a means to reconstruct complex genome regulatory processes when only genomic DNA is available. This project aims to develop effective computational approaches for reconstructing the chromatin structure of the genome solely from DNA methylation maps, in order to explore the complex regulatory processes that govern gene expression patterns in diverse human cell types, development, and in health and disease states.


Contact
Professor Ryan Lister - ryan.lister@uwa.edu.au 

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