Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

Funded PhD - FutureNeuro - Prof. David Henshall

This PhD project is an excellent opportunity to be involved in FutureNeuro - SFI Research Centre for neurological diseases.

Project description

FutureNeuro is a new national research centre focused on chronic and rare neurological diseases, funded by Science Foundation Ireland and based at the Royal College of Surgeons in Ireland (www.futureneurocentre.ie). FutureNeuro brings together multidisciplinary scientific teams with clinicians and industry to deliver advances in diagnostic medicine, personalized and network therapeutics, cross-linked by a national e-Health infrastructure platform that is disease-focused. 

We are now inviting applications for a PhD position available within the Centre. The PhD project will focus on molecular mechanisms, biomarkers and therapeutics for the neurological disease epilepsy. Aside from the core laboratory research project, your career development will be further supported by the Centre with training in entrepreneurship and science communication. In addition, you will be encouraged to gain industry experience by undertaking a three-month industry placement during your PhD programme. 

The PhD project: Characterization of RNA metabolism in paediatric epilepsy

Epilepsy is a common, chronic neurological disorder characterized by recurrent, unprovoked seizures. Current treatments fail at least one-third of patients and we have no disease-modifying therapies. This highlights a real unmet clinical need for a more in-depth understanding of the molecular mechanisms of epilepsy which will enable the development of novel, more efficacious therapies. The role of RNA in neurological disorders has garnered much attention recently as studies emerge (from our lab and others, see Jimenez-Mateos 2012, 2015; Reschke 2016; Mooney 2017) demonstrating an important regulatory role for different classes of RNA in conditions like epilepsy. Little, however, is known about the mechanisms by which RNA itself is regulated, and how these regulatory mechanisms enable pathogenic RNA activity. Key questions which will be addressed in this PhD project include, what are the mechanisms governing nascent RNA processing in neurons, through which molecules are these mechanisms mediated, and whether interfering with these processes may promote health and prevent epilepsy development. This project will specifically focus on RNA metabolism in severe childhood epilepsies for which there is a huge need for the development of anti-epileptic therapies. 

This PhD research project will involve a multi-disciplinary approach comprising neuroscience, genetics, RNA and protein chemistry and pharmacological tools to explore the molecular mechanisms governing RNA metabolism in epilepsy. The project will feature and require strong molecular biology skills and will utilize next-generation deep sequencing of RNA using state-of-the-art sequencing technologies and analysis tools. A translational research element will involve opportunities to analyze human brain samples from patients with epilepsy and feature the design and delivery of small molecule inhibitors to restore homeostatic neuronal RNA metabolism in vivo. The researcher will work with a highly dynamic team of neuroscientists based at the recently launched FutureNeuro Research Centre at RCSI and Trinity College Dublin as well as molecular biologists, clinicians and bioinformaticians and our broader network of scientific and clinical collaborators. 

Examples of recent relevant publications by FutureNeuro researchers and collaborators:

  • Reschke C et al. Potent anti-seizure effects of locked nucleic acid antagomirs targeting miR-134 in multiple mouse and rat models of epilepsy. Mol Thera Nucleic Acids 6, 45 – 56 (2017)
  • Henshall DC et al. MicroRNAs in epilepsy: pathophysiology and clinical utility. Lancet Neurol 15, 1368-1376 (2016)
  • Rajman et al. A microRNA-129-5p/Rbfox crosstalk coordinates homeostatic downscaling of excitatory synapses. EMBO J. 14;36(12):1770-1787 (2017)

Personal specification

The successful candidate should be able to demonstrate the following: 

Essential:

  • An Honours Bachelor degree (grade 2.1 or above) in a relevant discipline such as neuroscience, biochemistry, molecular biology, pharmacology, computer science, bioinformatics, statistics or genetics
  • Good communication skills
  • Strong organisational and administrative skills
  • Ability to work on one’s own initiative as well as in a multidisciplinary, team environment
  • Willingness to undertake training and career development
  • English language requirements for candidates who do not speak English as their first language: an IELTS score of 6.5 or above

Desirable:

  • Previous laboratory research experience  

Application process

Please apply here with the following:

  • an up-to-date CV
  • Application form (available from the application portal)
  • a 500-word cover letter outlining your interest in and suitability for the position
  • scanned transcripts (preferred), or detailed degree grade breakdown
  • contact details of two referees

Application deadline: Friday, 30 March 2018 at 5pm.

Interviews: April 2018

Start date: flexible 

Informal enquires to FN@rcsi.ie  

Mentors Prof. David Henshall