Epigenomics as the next step in molecular diagnostics

Applications are invited from suitably qualified candidates to join the RAPID Institute (Research Advances in Personalised Integrated Diagnostics) Research Group in DCU. The goal of our Institute is to understand and exploit the role of epigenetics in diseases that are particularly governed by temporal changes in the epigenome (e.g. Neurodegenerative & Metabolomic diseases/disorders. The RAPID Institute works across 3 distinct technology pillars/platforms (e.g. benchtop, portable and wearable diagnostic devices) to delve into the emerging power of epigenomics, explore biochemical wearable sensors, and enable POC settings with rapid, affordable testing. These platforms will be interconnected in a way that impacts epilepsy, substance abuse and infectious disease in unprecedented ways. 

This advertised PhD scholarship falls within research as part of Pillar 1 – Epigenomics as the next step in molecular diagnostics. PILLAR-1 will advance benchtop technologies using Lab-on-a-disc diagnostic devices, to enable users to probe the epigenome for diagnostic information without speciality labs, focusing on epilepsy and addictive behaviour. Epigenomics is the next step in DNA-based molecular diagnostics with recent research increasingly indicating that DNA methylation markers are likely to be important as biomarkers of clinical significance. The appointed PhD candidate will be hosted in the School of Biotechnology, Dublin City University and work under the supervision of the Principal Investigator Prof. James Landers, and co-supervised by members of the interdisciplinary research team (e.g. Drs Eadaoin Carthy, Loanda Cumba, David Kinahan, Nigel Kent, Margaret McCaul). We currently have a unique opportunity for the right candidate to avail of a full- time PhD Scholarship incorporating an annual tax-free stipend of €22,000, payment of EU tuition fees, and laptop. Travel to training, conferences and activities of the research will also be supported.

Project Background

Epigenomics has added a new dimension to DNA analysis highlighting the importance of reversible post-transcriptional modification. One modification is – DNA Methylation – a eukaryotic epigenetic mechanism where gene expression is altered through methylation of the C-5 location on cytosine immediately preceded by a guanidine residue – a ‘CpG site’ [1]. Recent research increasingly indicates that DNA methylation markers are likely to be important as biomarkers of clinical significance [2]. The state of methylation at any locus in the genome represents a snapshot in time of the dynamic changes that occur in the genome (not in base sequence) in response to an individual’s environment. These provide information on a vast array of phenotypes including ageing, diet, lifestyle, physiology, and even vitamin deficiency, to name a few [3]. It is clear that the ‘methylome’ contains an abundance of diagnostic information pertinent to a number of disorders [4], and an increasing number of DNA methylation-based biomarkers are being characterised with a particular focus on cancer. While only a small number have been FDA-approved to-date, these markers promise an additional biological dimension to non-invasive disease detection and monitoring [5]. While some clinical labs have the capability for methylated DNA analysis, it is not routinely incorporated into standard clinical testing. In the absence of a reliable, easy-to-use method for methylation biomarker analysis in a clinical or research lab setting, there is a clear need for a cost-effective, flexible diagnostic device platform, capable of being used for diverse biomarker panels, and designed to integrate into current clinical lab workflows. We will address this directly to open up new vistas in genome-based biomarker detection that can easily be incorporated into current clinical lab workflows.

The proposed research will build on core centrifugal Lab-on-a-Disc (LoaD) technologies developed by both Prof. Landers and other members of our interdisciplinary research team to achieve (i) miniaturisation of the cumbersome sample preparation associated with DNA methylation quantitation and (ii) integration the entire workflow through to Sanger sequencing. The first part involves microfluidic on-disc integration of required chemistries using a CD-sized multilayered centrifugal disc. Fluid flow is driven centrifugally, with the unit operations (e.g., liquid transport, mixing, aliquoting, heating and washing) facilitated by spin speed and laser valving [6]. The second part involves extending the disc to incorporate PCR and Sanger sequencing. We have demonstrated rapid microscale PCR with heating via Peltiers [7], infrared light [8], microwaves [9], and will exploit our existing faSTR system where ultrafast PCR (20 min) was integrated for amplification of target sequences from 10 genetic loci [10]. Two relevant and cutting-edge applications areas will be pursued, depending on the candidate profile and interest, specifically (a) ‘Epigenome diagnostics’ For Classifying Types of Epilepsy or (b) Epigenomic Signatures for drug abuse.

Person Specifications

Minimum Criteria

• Have an Upper Second Class (2.1) honours degree (or equivalent).

• A Master’s degree or other post graduate qualification in a relevant subject and/or research area is desirable. A research master’s degree in Lab-on-a-Chip or other areas related to Pillar 1 activities are particularly welcome.

• Have experience of qualitative and/or quantitative research methodologies.

• Demonstrate themselves to be highly motivated, with strong organisational, interpersonal and (oral/written) communication skills.

Desirable Criteria

• Experience in microfluidics / Lab-on-a-Chip and/or common biochemical and molecular biology (nucleic acid) techniques/methods is highly desirable.

• Experience working /conducting academic empirical research.

• Previous experience in health-related research would be beneficial to the post.

• Have presented their research findings, either at national/international conferences or in peer-reviewed journals.

Application Process

Applications to include CV, covering letter (demonstrating how you fulfil the essential and desirable criteria), and the contact details of two referees should be sent, via e-mail (in word or PDF only) to Dr John Gleeson at john.p.gleeson@dcu.ie.

Closing date for receipt of applications is 19th July 2024.