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High Resolution Microscopy in the DNA Damage Response

Final Report Summary - IMAGE DDR (High Resolution Microscopy in the DNA Damage Response)

Scientific Background:

Our hereditary information is encoded in DNA, which is intrinsically vulnerable to alteration, being damaged by multiple agents (both endogenous and exogenous) while also being susceptible to change during duplication. Cells spend a significant proportion of their energy maintaining the integrity of their DNA: multiple repair pathways recognise and fix DNA damage and these are closely integrated with the DNA replication procedure, which is highly sophisticated in order to ensure accurate and correctly timed duplication. Linking into and between these intricate mechanisms are surveillance pathways and quality controls that continuously detect problems and modify the cellular status to optimise opportunities for remedial action, or, when appropriate, divert cells into death pathways so that further proliferation is prevented. Advanced microscopy is particularly well suited for application to the field, but within the European Research Area (ERA) there is a paucity of trained individuals with a deep understanding of the traditional molecular and cellular approaches to genome stability research combined with experience in advanced microscopy.


Training Background:

The Initial Training Network (ITN) "High Resolution Microscopy in the DNA damage Response (Image DDR) aimed to address the European structural deficit in post-doctoral researchers who are able to integrate advanced microscopy in the study of the DNA Damage Response (DDR) and genome stability fields. To achieve this we created a network of collaborating laboratories and an SME. Our aim was to providing 10 Early Stage Researchers (ESRs) with cross-disciplinary training in state-of-the art imaging methodology alongside the traditional approaches to the field, namely molecular and classical genetics, biochemistry and cellular studies. The provision of such cross-disciplinary training within a network integrating cross-sectorial experience was further designed to provide the students with a distinct career advantage based on their training. To provide a clear routes to cross-disciplinary training, the network was carefully constructed to contain four local nodes. Each local node contained two laboratories with complementary expertise (imaging and traditional biology). Students could thus work seamlessly between disciplines in the context of a wider network. The advantages of the wider network (shared experience within and across sectors plus an extensive technical expertise) would be exploited by the students through both formal ITN training events and informal/bespoke collaborations.


Partners:

Partner 1 (2 laboratories; local node A): University of Sussex, United Kingdom (2 ESRs). Partner 2 (2 laboratories; local node B): Institut Curie, France (2 ESRs). Partner 3 (1 laboratory; part of local node C): Friedrich Miescher Institut, Switzerland (1 ESR). Partner 4 (1 laboratory; part of local node C): University of Milano-Bicocca, Italy (1 ESR). Partner 5 (2 laboratories; local node D) Ben-Gurion University, Israel (2 ESRs). Partner 6 (Industrial sector representative): Genomic Vision, France (2 ESR)



Training implementation:

For each ESR, laboratory skills training was provided by the host laboratory. Cross-disciplinary training was provided within 4 local nodes of the ITN. Cross-sectorial experience was provided by interactions between the academic and industrial partners. Each academically based ESR was seconded to the SME. Formal training was provided by Network-wide events that were established and organised with the help of the Fellows. Coherence within the day-to-day experimental training for each ESR and integration of network events into the needs and expectation of the ESRs was ensured by an Individual Training Plan (ITP) prepared in consultation with the ESR and formally ratified by than Oversight Committee. This was also was used by a Training Committee to benchmark ESR progress on a six monthly basis.


Progress in training:

10 ESRs were recruited. In addition to laboratory projects and attendance of external meetings, their training was supplemented by ITN workshops on advanced microscopy and ITN meetings focusing on the underlying science and methodologies. Four Fellows have completed their training, written and defended their PhDs. Of these 3 have secured postdoctoral positions and one has secured a position in the industrial sector. Three Fellows have finished their training and are currently writing their PhD. Each is actively seeking a postdoctoral position. Recruitment delays mean that three Fellows remain in training. Their host institutions have agreed funding to ensure completion. All Fellows have contributed to preparing data for publication.

Scientific progress:

Scientific progress has been excellent. The milestones set have been passed and the scientific deliverables achieved. All Fellows either have already authored scientific papers or are preparing manuscripts for submission.


Socio-economic impact:

The IMAGE DDR ITN has contributed to strengthening of the research potential of the ERA by training 10 ESRs in cross disciplinary research and providing cross-sectorial experience that will contribute to the future exploitation of biotechnology. By pursuing excellent science, the network has contributed to the overall scientific knowledge of an important area of science underpinning treatment of a major human disease, cancer.

Six of the 10 ESRs recruited were woman, underpinning the aim of the EU to improve gender balance in science. The ITN was comprised of nine laboratories, of which 5 were led by female investigators, providing excellent role models for ESRs. A deliberate and successful collateral outcome of the ITN has been mentoring of junior female lab leaders by senior female colleagues.

Concluding remarks

The ITN has been a significant success and has achieved its training objectives by providing 10 ESRs with expertise in state-of-the-art microscopy and imaging in addition to a solid understanding of traditional molecular biology and genetics approaches. Success is exemplified by the outcome. All ESRs have either completed or are on course to complete a PhD. Of the four who have so far been awarded their PhD, all have excellent and appropriate jobs. Three fellows are preparing to submit their PhD thesis. Three ESRs have yet to complete their training. The commitment of the partners will ensured that each of these ESRs will be fully funded to complete their training with the support of the network.

Contact: Antony Carr, Network coordinator. a.m.carr@sussex.ac.uk. GDSC, University of Sussex, Brighton, BN1 9RQ, UK

The network website, which was unfortunately hacked disabled and destroyed, has been re-established with a new domain name: http://mariecurieimageddr.org.uk.