Dr Joe Rainger (UKRI Future Leaders Fellow)

Roslin Research Fellow

Biography

Background

Joe Rainger is a UKRI Future Leaders Fellow (Round 2), Roslin Institute Fellow, and a University of Edinburgh ESAT Fellow. His research group aims to understand the complex processes that underly embryonic tissue fusion processes, with particular emphasis on ocular coloboma. His group has with overlapping interests in broader aspects of vertebrate development and the causes of ocular malformations. Joe is based at Roslin Institute, where he came in 2015 after winning a Fight for Sight Early Career Investigator fellowship. 

Research Interests

The Rainger group’s research is focused on understanding the genetic, molecular and cell-behavioural aspects that underpin fusion of tissues in the developing retina, and uses chicken embryology as a key experimental model system. Current focus is placed upon revealing specificities of gene transcription at defined stages of tissue fusion, and revealing the regulatory networks that control these transcriptional responses. This is combined with studies of intra- and inter-cellular molecular interactions and dynamic cell behaviours, and exploring the influence of non-genetic factors that may affect tissue fusion. Use is made of transgenic chicken lines from the National Avian Research Facility (NARF, Roslin Institute) and the development of novel transgenic resources to further understanding of tissue fusion mechanisms in the eye and other embryonic regions. Collaborations with clinical paediatricians and ophthalmologists are welcome to support the identification and experimental validation of causative genetic mutations in patients and families affected by a wide range of tissue fusion defects.

Research summary

Our group investigates epithelial tissue fusion and related human disorders. Disruptions to how tissues fuse together during human development is a common cause of birth defects, affecting approximately 1 in 500 people in the UK. Our research has been prompted because despite our best efforts, most patients born with problems such as cleft palate, spina bifida, and heart defects still don't have the genetic cause of their disorder identified. This often impacts genetic counselling and efforts towards prevention. We also remain unsure what impacts maternal environment have on these conditions (e.g. illness, vitamin deficiency, or substance abuse). We aim to address these by performing transformative research to reveal the key genes, cell behaviours, and molecular systems required for normal tissue fusion, and provide a step-change in our knowledge of how these can be perturbed.

Current research interests

Aim 1. Define the inherent cell characteristics during fusion at the molecular and behaviour levels. To understand the basis of fusion at the molecular level, we are comprehensively defining the genetic and protein-marker signatures of cells directly mediating fusion, and how these change as fusion progresses. We have developed gene-edited chicken lines which enable us to selectively isolate cells as they mediate fusion. These are being applied in normal and defective tissue fusion contexts to identify key markers and gene expression dynamics for these cells, and to link these to cell behaviours and epithelial remodelling during and after fusion. Aim 2. Define the functional roles for an evolutionarily conserved mediator of fusion. We recently showed that Netrin-1 (encoded by the NTN1 gene) is a specific marker for cells mediating fusion in the eye, and that loss of Netrin-1 causes multi-system fusion defects in other tissues. NTN1 is also expressed in a range of human cancers. We have generated genetic models of NTN1 perturbation during fusion in the embryonic chick eye to test its functional role. We are assessing changes to gene-expression and the molecular and cell-behaviour of cells in the fusion environment, and the impact on basement membrane dynamics and integrity. We use a combination of approaches, including bulk and single-nuclei RNAseq, ATACseq, proteomics, alongside spatial gene expression analyses (RNAscope, HCR) and standard immunofluorescence and complementary cell culture systems. We are also making use of transient and germ-line gene editing technologies in the chicken. We are developing ex vivo culture systems for live-imaging of fusion in the chicken embryo and excised tissues. We are also keen to utilise the experimental tractability of chick embryology to explore environmental influences on fusion-specific gene expression to link maternal factors to tissue fusion biology. We welcome collaborative enquiries from other tissue fusion biologists and those with an interest in developmental EMT and the effects of environment on embryonic development. We also are keen to work with clinicians who have interests in the disease mechanisms and genetics of tissue fusion disorders. We encourage researchers at any career stage to make contact if they would like to work in our team.

Project activity

 

  • UKRI Future Leaders Fellowship (renewal): Novel approaches to define tissue fusion mechanisms in embryonic development. £699,958 MR/X014339/1; 1/09/23 → 31/08/26. PI
  • ISP22 Pump-priming: Spatial profiling of protein in situ-optimisation of mass spectrometry imaging. £2,380 BBSRC (internal). 1/09/22 → 31/03/23. PI
  • UKRI Future Leaders Fellowship: Novel approaches to define tissue fusion mechanisms in embryonic development. £1,092,772. MR/S033165/1; 1/09/19 → 31/08/23. PI
  • FTMA 3: Immersive training in scanning serial block face electron microscopy. £2,380 BBSRC (internal). 1/12/21 → 31/03/22. Co-I (returned unused)
  • BBSRC Capital Equipment Bid: “Integrated Tissue Phenotyping Platform”. £4,200,000 (component of £10M award). 24/11/2020 → 31/03/2025.
  • ISP18 Pump-priming: Definition of Enhancer-Promoter Interactions in the Chicken. £20,000 BBSRC (internal) 1/11/18 → 31/07/19. Co-I

Current project grants

• UKRI Future Leaders Fellowship (renewal): Novel approaches to define tissue fusion mechanisms in embryonic development. £699,958 MR/X014339/1; 1/09/23 → 31/08/26. PI
• ISP22 Pump-priming: Spatial profiling of protein in situ-optimisation of mass spectrometry imaging. £2,380 BBSRC (internal). 1/09/22 → 31/03/23. PI
• UKRI Future Leaders Fellowship: Novel approaches to define tissue fusion mechanisms in embryonic development. £1,092,772. MR/S033165/1; 1/09/19 → 31/08/23. PI
• FTMA 3: Immersive training in scanning serial block face electron microscopy. £2,380 BBSRC (internal). 1/12/21 → 31/03/22. Co-I (returned unused)
• BBSRC Capital Equipment Bid: “Integrated Tissue Phenotyping Platform”. £4,200,000 (component of £10M award). 24/11/2020 → 31/03/2025.
• ISP18 Pump-priming: Definition of Enhancer-Promoter Interactions in the Chicken. £20,000 BBSRC (internal) 1/11/18 → 31/07/19. Co-I

Past project grants

• Fight For Sight Early Career Fellowship: Elucidating the genetic and molecular causes of ocular coloboma. £199,998 Ref#1590/1591; 1/10/2015 → 30/09/2018. PI
• Institutional Strategic Support Fund (ISSF3) award: Genetic manipulation of the developing chick eye to understand mechanisms of optic fissure closure. £35,000. 20182019. PI

View all 23 publications on Research Explorer

Invited speaker

 

  • International Federation of Anatomy Association, 6th annual Programme on International Research (2022).
  • The Macular Society meeting: Gene editing in Ophthalmology. Oxford University (2022)
  • ARVO 2022 Special Session: Gene editing technologies. Denver, Colorado. (2022)
  • CMVM AWERB away day - guest scientist talk (2022)
  • EGGEd Workshop, Edinburgh. (2022)
  • Avian Research Symposium (2021)
  • UK Chick Developmental Biology Meeting (2021).
  • Invited external Seminar Speaker - University of East Anglia (2021)
  • The Macular Society meeting: Gene editing in Opthalmology. Oxford University (2021)
  • Selected abstract: Company of Biologists Autumn Meeting (2021)
This article was published on