Andrew Jackson Research Group
Mechanisms for Microcephaly, Cancer and Autoinflammation
Section: Disease Mechanisms
Research in a Nutshell
This programme identifies genes causing inherited disorders of the brain. We study how these genes function, using cells and model organisms.
Aicardi-Goutières syndrome is a genetic condition in which faults in genes encoding enzymes called nucleases mimic viral infection of the brain. These nucleases may normally clean up naturally produced ‘waste’ DNA and RNA. Failure of this process leads to the body mounting an immune reaction against itself. This immune response mechanism is relevant to common autoimmune diseases such as lupus. So, we are studying these nucleases to understand their normal roles in cells and to establish what happens when these enzymes fail.
From studying one of these nucleases, we have found that ribonucleotides, the building blocks of RNA, are also present in DNA. They can be harmful causing damage to the genome and can lead to mutations in cancers. The signature of such mutations may be useful in future in tailoring cancer therapies.
We also discover genes that cause primordial dwarfism, conditions with extreme growth failure of the brain and body. Such individuals are the 'smallest people in the world'. These disorders are due to fewer cells being made during development, leading to a smaller person. Identifying primordial dwarfism genes helps diagnose and manage these rare conditions. It also gives insights into how the body regulates growth, perhaps shedding light into why humans are bigger than mice and how our brains evolved to be so large.
People |
|
|---|---|
| Professor Andrew Jackson FRS | Group Leader |
| Colin Stok | Postdoctoral Researcher |
| Maggie MacDonald | Research Coordinator |
| Paula Carroll | Research Technician |
| Martin Reijns | Senior Postdoctoral Researcher |
| Diana Rios Szwed | Postdoctoral Researcher |
| Andrea Robertson | Senior Research Technician and Area Supervisor |
| Lukas Tamayo Orrego | Postdoctoral Researcher |
| David Parry | Postdoctoral Researcher |
| Carol-Anne Martin | Postdoctoral Researcher |
| Gráinne Neary | ECAT-V Clinical Lecturer/PhD student |
Contact
Publications
- Signatures of TOP1 transcription-associated mutagenesis in cancer and germline Reijns et al, Nature 2022
- A sensitive and affordable multiplex RT-qPCR assay for SARS-CoV-2 detection Reijns et al, Plos Biology 2020
- Gain of function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of polycomb-regulated regions Heyn et al, Nature Genetics 2019
- CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions Zimmermann et al, Nature 2019
- cGAS surveillance of micronuclei links genome instability to innate immunity Mackenzie et al, Nature 2017
Collaborations
- Professor Martin Taylor, MRC HGU, University of Edinburgh
- Professor Yanick Crow, MRC HGU, University of Edinburgh
- Dr Duncan Sproul, MRC HGU, University of Edinburgh
- Dr Tom Deegan, MRC HGU, University of Edinburgh
- Professor Nick Gilbert, MRC HGU, University of Edinburgh
- Professor Javier Caceres, MRC HGU, University of Edinburgh
- Dr Andrew Wood, MRC HGU, University of Edinburgh
- Dr Tamir Chandra, MRC HGU, University of Edinburgh
- Dr Joe Marsh, MRC HGU, University of Edinburgh
- Dr Ailith Ewing, MRC HGU, University of Edinburgh
- Dr Luke Boulter, MRC HGU, University of Edinburgh
- Professor Neil Henderson, MRC HGU (affiliate), CIR, University of Edinburgh
- Dr David Hunt, DRI, University of Edinburgh
- Professor Elaine Dzierzak, QMRI, University of Edinburgh
- Professor Grant Stewart, University of Birmingham
- Professor Dan Durocher, University of Toronto
- Professor Ian Hickson, University of Copenhagen
- Professor Simon Boulton, Crick Institute, London
- Dr Jan Rehwinkel, WIMM, Oxford
- Dr Tuncay Baubec, Zurich
- Professor Kamil Kranc, Queen Mary University, London
- Professor Tatjana Stankovic, Birmingham
- Dr Mike Bober, Delaware
- Dr Carol Wise, Dallas
- Professor Bernd Wollnik, Gottingen
- Professor Valerie Cormier-Daire, Paris
- Walking with Giants Foundation, UK
- Potentials Foundation, USA
Partners and Funders
- Medical Research Council
- European Research Council
- EMBO
Scientific Themes
Microcephaly, Aicardi-Goutieres syndrome, Ribonuclease H2, genome stability, inflammation, cancer