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

Four funded PhDs - FutureNeuro - Prof. David Henshall and Prof. Gianpiero Cavalleri

These PhD projects are an excellent opportunity to be involved in FutureNeuro - SFI Research Centre for neurological diseases.

Project description

Up to one billion people worldwide suffer from brain diseases. In Europe, brain diseases represent 35% of the total burden of all disease, affecting 179 million patients and costing more than €800 billion per annum. Neuroscience and genetics research underpinned by remarkable new technologies have advanced our understanding of the pathomechanisms of these diseases. There remains, however, an enormous gap in translation to patient care, where the current system for diagnosing, treating and managing chronic and rare neurological diseases is inadequate and fails patients.

Science Foundation Ireland (SFI) has recently funded FutureNeuro – a National Research Centre of Excellence for chronic and rare neurological diseases based at RCSI. FutureNeuro brings together multidisciplinary scientific teams with clinicians and industry to deliver advances in diagnostic medicine, personalised and network therapeutics, cross-linked by a national e-Health infrastructure platform that is disease-focused. The mission of FutureNeuro is to accelerate discoveries on genetic diagnosis and advanced molecular treatments supported by enabling e-health technology for chronic and rare neurological diseases.

Under the programme there will be an initial intake of up to four PhD positions with a student stipend of €18,500. Aside from the core laboratory research project, your career development will be further supported under 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.

Read more about FutureNeuro and the projects available here.  

 

The PhD projects

FN01 Investigating the role of rare, functional genetic variation on psychosis and mood disorders in epilepsy.

Led by Prof. Cavalleri, the Human Genetic Variation Research Group at RCSI is exploring how genetic variation can guide the treatment of complex neurological conditions such as epilepsy. Some patients with epilepsy also have psychosis as a co-morbidity. Others develop acute psychosis as an adverse reaction to particular anti-epileptic drugs. This project will, building on analysis conducted by our research group in collaboration with others, explore the genetic component to psychosis as a co-morbidity of epilepsy, and as an adverse reaction to anti-epileptic drugs. The project will facilitate the doctoral student to develop valuable skills in the generation, handling and analysis of genomic-level next-generation DNA sequence data. Such skills are currently in high demand in both academia and the pharma industry, as next-generation sequencing transforms our understanding of the genetics of complex human traits.

 

FN02 Exploring novel roles for noncoding RNAs as drug targets and biomarkers of epilepsies.

Research by the Henshall laboratory and collaborators has identified important roles for small noncoding RNAs called microRNAs in the development of epilepsy and suggested they may have therapeutic and diagnostic potential. This project will characterise novel noncoding RNAs within biofluids and brain samples in patients with epilepsy. The project will involve close collaboration with clinicians and experimental techniques including sequencing and bioinformatics analysis of small noncoding RNAs as well as cell and molecular assays to determine their molecular functions and mechanisms.

 

FN03 Neuron-glia cross-talk via purinergic signaling in epilepsy.

ATP is released by neurons and glia to function in modulating synaptic strength and neuroinflammatory responses to brain injury. This project will use genetic tools including viral vectors and transgenic reporter mice to define the mechanisms involved in neuron-glia neuroinflammatory signaling mediated by purines in epilepsy. The research will also test pharmacologic and genetic manipulations of this transmitter system in models of epilepsy and human neurons.

 

FN04 Novel molecular mediators of the anti-convulsant actions of cannabinoids.

Cannabinoids have recently emerged as novel therapeutics for certain devastating epilepsies of childhood including Dravet syndrome. This project will focus on exploring the molecular mechanisms underlying these effects. The research will feature a strong focus on pharmacology, cell and electrophysiological assays of neuronal network behaviour and in vitro and in vivo models of epilepsy. 

 

Examples of recent relevant publications by the RCSI teams and their collaborators:

  • Epi4K consortium; Epilepsy Phenome/Genome Project. Ultra-rare genetic variation in common epilepsies: a case-control sequencing study. Lancet Neurol. 2017 Feb;16(2):135-143.
  • Rajman et al. A microRNA-129-5p-Rbfox cross-talk coordinates homeostatic down-scaling of excitatory synapses. EMBO Journal (2017) doi: 10.15252/embj.201695748
  • Reschke 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)
  • Jimenez-Pacheco et al. Transient P2X7 receptor antagonism produces lasting reductions in spontaneous seizures and gliosis in experimental temporal lobe epilepsy. Journal of Neuroscience 36, 5920-5932 (2016)

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 for FN01: Friday, 14 July 2017 at 5pm.

Application deadline for FN02, 03 and 04: Friday, 30 June 2017 at 5pm.

Interviews: July/August 2017

Informal enquires to FN@rcsi.ie  

Mentors Prof. David Henshall and Prof. Gianpiero Cavalleri