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The role of endogenous retroviruses in human health and disease

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Awaiting Funding Decision/Possible External Funding
    Awaiting Funding Decision/Possible External Funding

Project Description

More than 10 years have passed since the first high quality (nearly) complete version of the human genome and we are still exploring its functionality. The most well-studied part is the one that encodes for proteins (known as exome) and accounts for 2-3%. The rest of the genome is much less understood. Around half is comprised of repetitive elements that have been replicated by "copy-paste" mechanisms. One category of them, known as Endogenous Retroviruses (ERVs), are remnants of ancient retroviral infections of our deep-in-time ancestors’s germ-cells, and comprise around 5-8% of the human genome. A pathophysiological role has been described for some of them, for example the well-studied "humanized" syncytin genes. In a recent study ERV RNA was shown to be a marker of the stem-cell identity. Nevertheless, researchers have hypothesized for many years that some ERVs play a role in the development of diseases such as cancer and autoimmunity with no clear results in humans.

Most of the ERVs found in the genome of modern humans have not proliferated since 10 million years ago. The exception is one specific ERV known as HERV-K HML-2 (HK2) the present day activity of which cannot be excluded. In fact we provide evidence that the possibility of proliferation in the germline of modern human populations is significant. We know that these retroviruses have a preference to go near genes and we showed that this process is likely to have a pathogenic result.

Our main questions is how HK2 contributes in pathogenesis in humans.

We seek a highly motivated individual with passion for research.

The successful applicant is expected to:
1) develop skills in human genomics and high throughput sequencing applications/bioinformatics
2) analyse Big Data such as datasets available from the 100,000 genomes project
3) be trained in retrovirology
4) develop science communication skills
5) write first-author research papers

We are devoted in providing world-class research training.

Our group is one of the leading research groups in the field of human endogenous retroviruses with ongoing collaborations with research groups at the University of Oxford, Imperial College, as well as the United States. Our research has been frequently covered by international media:

-CNN: “Addiction could stem from ancient retrovirus, study suggests” (September 2018)
(https://edition.cnn.com/2018/09/25/health/retrovirus-addiction-study-intl/index.html)
-Reuters: “Conflict in Ukraine escalated spread of HIV – scientists” (January 2018)
(https://www.reuters.com/article/ukraine-hiv/conflict-in-ukraine-escalated-spread-of-hiv-scientists-idUSL8N1P74IT)
-New York Times: “Ancient Viruses Are Buried in Your DNA” (October 2017)
(https://www.nytimes.com/2017/10/04/science/ancient-viruses-dna-genome.html)
-UNAIDS Science Now: “Needle-syringe programmes and treatment will dramatically reduce HIV epidemic among people who inject drugs in Russia and Ukraine” (December 2016)
(https://sciencenow.unaids.org/post/key-populations-23)
-CNN: “How HIV Spread Across the West” (07/2016)
(http://edition.cnn.com/2016/07/07/health/global-spread-of-hiv/)
-National Geographic: “Our Inner Viruses: Forty Million Years In the Making” (02/02/2015)
(http://phenomena.nationalgeographic.com/2015/02/01/our-inner-viruses-forty-million-years-in-the-making/)
-BBC News: Hepatitis C: New drug treatment ’is a breakthrough’ (12/04/2014)
(http://www.bbc.co.uk/news/health-26987653)
-New Scientist: Neanderthal virus DNA spotted hiding in modern humans (21/11/2013)
(http://www.newscientist.com/article/dn24598-neanderthal-virus-dna-spotted-hiding-in-modern-humans.html)
-BBC News: Spread of Hepatitis C pinpointed (01/02/2013)
(http://www.bbc.co.uk/news/health-21282381)
-BBC News: Ancient virus DNA thrives in us (24/04/2012)
(http://www.bbc.co.uk/news/science-environment-17809503)

Funding Notes

We are currently looking for:
1) self-funded applicants. Note that successful applicants will not have to cover for University or bench fees.
2) students willing to apply for external studentships. Applicants need to fully analyse their plans for external applications.

We are also happy to support applications for Greek-state studentships. However applicants should note that Greek-state studentships are available only after successful application and school admission. Thus applicants seeking to get support from the Greek-state should be willing to engage with the PhD project and cover their expenses until their Greek-state studentship application becomes successful.

References

-Human Endogenous Retrovirus-K HML-2 integration within RASGRF2 is associated with intravenous drug abuse and modulates transcription in a cell-line model. Karamitros T, Hurst T, Marchi E, Karamichali E, Georgopoulou U, Mentis A, Riepsaame J, Lin A, Paraskevis D, Hatzakis A, McLauchlan J, Katzourakis A, Magiorkinis G. Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10434-10439. doi: 10.1073/pnas.1811940115. Epub 2018 Sep 24

-Transcriptional Modulation of Human Endogenous Retroviruses in Primary CD4+ T Cells Following Vorinostat Treatment. White CH, Beliakova-Bethell N, Lada SM, Breen MS, Hurst TP, Spina CA, Richman DD, Frater J, Magiorkinis G, Woelk CH. Front Immunol. 2018 Apr 12;9:603. doi: 10.3389/fimmu.2018.00603. eCollection 2018.

-Roles of Endogenous Retroviruses in Early Life Events. Magiorkinis G, Katzourakis A, Lagiou P. Trends Microbiol. 2017 Nov;25(11):876-877. doi: 10.1016/j.tim.2017.09.002. Epub 2017 Sep 29

-STEAK: A specific tool for transposable elements and retrovirus detection in high-throughput sequencing data. Santander CG, Gambron P, Marchi E, Karamitros T, Katzourakis A, Magiorkinis G. Virus Evol. 2017 Aug 21;3(2):vex023. doi: 10.1093/ve/vex023. eCollection 2017 Jul.

-Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency. Hurst T, Pace M, Katzourakis A, Phillips R, Klenerman P, Frater J, Magiorkinis G. Retrovirology. 2016 Feb 6;13:10. doi: 10.1186/s12977-016-0242-4.

-Unfixed endogenous retroviral insertions in the human population. Marchi E, Kanapin A, Magiorkinis G, Belshaw R. J Virol. 2014 Sep 1;88(17):9529-37. doi: 10.1128/JVI.00919-14. Epub 2014 Jun 11

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