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Investigating the roles of endogenous retroviruses in the human placenta

Code: BC-DTP_2026_38

Title: Investigating the roles of endogenous retroviruses in the human placenta

Primary Supervisor: Miguel Branco

Email: m.branco@qmul.ac.uk

Institute: Blizard Institute

Secondary Supervisor: Lovorka Stojic

Email: l.stojic@qmul.ac.uk

Institute: Barts Cancer Institute

Lay Summary:

The placenta is a remarkable organ that performs a variety of important functions during pregnancy. It supports the development of the fetus and also helps prepare the mother’s body for pregnancy. When there are problems with the placenta, the development of the baby can be compromised, leading to undesirable pregnancy outcomes such as growth restriction or preterm birth. Placental dysfunction can also affect the mother, namely in a hypertensive disorder called preeclampsia. Most pregnancy complications are more frequent in East London populations. 
 
Our understanding of how placental function is controlled remains limited, and thus so does our ability to develop effective treatments that prevent pregnancy complications. Whilst most research to date has focused on how genes regulate the placenta, these only account for a very small fraction of our genome. We propose to investigate a neglected, yet more abundant part of our genome that could play important roles in human pregnancy: endogenous retroviruses (ERVs). Remarkably, ERVs used to be viruses that became part of our genome millions of years ago. Recent research has been revealing that they often play important roles in health and disease. 
 
We propose to survey the activity of ERVs in the human placenta and then use state-of-the art in vitro methods to understand what their roles are and how they perform those roles. We will then ask whether the dysregulation of these ERVs is linked to pregnancy complications. This will create novel opportunities to predict pregnancy complications early on and to develop new treatment strategies. 

Aims:
The overarching objective of this project is to test the functional significance of ERV expression in human trophoblast. We will use a combination of computational approaches, manipulation of 2D and 3D culture models, and biochemistry to ask how the regulatory and coding potential of ERVs affects cellular phenotypes in trophoblast. Specifically, we aim to: 

  1. Perform a detailed characterisation of ERV expression in human trophoblast
  2. Test the transcriptional and phenotypic impact of depleting selected ERVs
  3. Dissect the mechanisms underlying ERV function in trophoblast
  4. Assess the potential involvement of ERV deregulation in pregnancy complications

References:

1. Brosens et al (2011) Am J Obstet Gynecol, 204, 193-201 
2. Senft & Macfarlan (2021) Nat Rev Genet, 22, 691-711 
3. Lavialle et al (2013) Phil Trans R Soc B, 368, 20120507 
4. Frost et al (2023) Nat Struct & Mol Biol, 30, 527-538 
5. Kong et al (2024) PNAS, 121, e2318176121 
6. Okae et al (2018) Cell Stem Cell, 22, 50-63.e6 
7. Turco et al (2018) Nature, 564, 263-267 
8. Dodel et al (2024) Nat Methods, 21, 423-434

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