Ageing and non-coding RNA: does the thirst for ribosomes control lifespan?
Lead Research Organisation:
University of Cambridge
Department Name: Plant Sciences
Abstract
Ageing is almost universal in eukaryotes and dissecting pathways that modulate ageing in simple tractable organisms will provide clues to the drivers of human ageing. Although ageing appears inevitable, genetic studies have revealed pathways that strongly influence the rate of ageing. In fact, many of these pathways converge on a highly conserved process: ribosome synthesis. Cells need a huge amount of ribosomes to meet protein synthesis requirements and devote vast resources to synthesising ribosomes. To meet this demand, genomes contain hundreds of copies of the genes encoding ribosomal (rRNA), organised in tandem arrays called ribosomal DNA (rDNA). The number of rDNA copies is variable, and we have recently shown that a key pathway which modulates ageing in yeast also controls amplification of rRNA genes in response to the environment. This raises the exciting idea that ageing may be driven by the cellular demand for ribosome synthesis, a highly conserved but controllable process. Surprisingly, the effects of ribosome synthesis and rDNA copy number on ageing are almost completely unstudied in multicellular organisms. We think that individual variability is crucial to understanding ageing and rDNA copy number varies dramatically between individuals. Therefore, the aim of this project is to elucidate how ribosome synthesis influences ageing in individual worms. Worms are an excellent model organism for ageing due to their short natural lifespan and experimental tractability. This project would extend into a PhD aimed at understanding how ageing and stress resistance are impacted by the massive but variable resource consumption of ribosome synthesis.
Organisations
People |
ORCID iD |
Jonathan Houseley (Primary Supervisor) | |
Andre Zylstra (Student) |
Publications
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/M011194/1 | 30/09/2015 | 31/03/2024 | |||
1645489 | Studentship | BB/M011194/1 | 30/09/2015 | 29/09/2019 | Andre Zylstra |
Description | 1) Ribosomal DNA copy number variation has minor effects on transcriptomes and phenotypes We performed transcriptomic (RNA sequencing) and phenotypic studies to determine whether there were population-level effects of large ribosomal DNA (rDNA) copy number changes in nematode worms (Caenorhabditis elegans) and budding yeast (Saccharomyces cerevisiae). These analyses generally found minimal impact from rDNA copy number in either species. 2) rDNA circle accumulation is not required for several known yeast ageing phenotypes As yeast cells age they accumulate circles of DNA from a specific repetitive region of the genome. These are called extrachromosomal ribosomal DNA circles (ERCs). Research from other labs recently provided very strong evidence that ERC accumulation immediately precedes severe late life pathological changes in ageing yeast. However, there are various physiological changes which occur during ageing yeast and it is not known whether ERC accumulation is necessary or sufficient for each of these changes to occur. We used RNA sequencing to profile gene expression from a time course of ageing yeast samples, comparing data from wild type yeast and mutants with drastically reduced ERC accumulation. This analysis revealed that several known ageing phenotypes occur largely independent of age-related ERC accumulation. This is of interest beyond just the yeast ageing field. Study of yeast ageing is considered valuable because there are similarities in the biochemical and cellular changes occurring during yeast and human ageing. Importantly, we have shown that ERC accumulation (considered relatively yeast-specific) is not required for age-related changes, particularly in gene expression. This bolsters the hope that human-relevant insights about the ageing process can be determined from yeast work as it remains plausible that conserved mechanisms are at work. |
Exploitation Route | This work will be published in my PhD thesis. The work supported by this award is expected to be published with similar data in a scientific journal article later this year. It will be of immediate use for other workers in the yeast ageing field. |
Sectors | Other |
Description | Conference Poster Presentation & Flash Talk - RNA UK 2020 conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | I presented a scientific poster on current findings from work supported by the award. This included several interesting disussions with other researchers. |
Year(s) Of Engagement Activity | 2020 |
Description | Conference Poster Presentation - BSRA Meeting: The Biology of Ageing and the Omics Revolution |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | I presented a scientific poster on current findings from work supported by the award. This included several interesting disussions with other researchers. |
Year(s) Of Engagement Activity | 2017 |
Description | Conference Poster Presentation - EMBO C. elegans development, cell biology and gene expression conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | I presented a scientific poster on current findings from work supported by the award. This included several interesting disussions with other researchers. |
Year(s) Of Engagement Activity | 2018 |
Description | Host lab for BI Schools Day 2017 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | School visit to institute, children performed some experiments for a day |
Year(s) Of Engagement Activity | 2017 |
Description | Host lab for BI Schools Day 2018 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Groups of schoolchildren and teachers were hosted in my lab for a day to perform experiments and learn about research careers. |
Year(s) Of Engagement Activity | 2018 |
Description | Host lab for BI Schools Day 2019 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Groups of schoolchildren and teachers were hosted in my lab for a day to perform experiments and learn about research careers. |
Year(s) Of Engagement Activity | 2019 |
Description | Lifelab - DH, AZ and AW |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Together with the Wellcome Genome Campus, European Molecular Biology Laboratory European Bioinformatics Institute, the University of Cambridge and the Medical Research Council Laboratory for Molecular Biology, the Institute organised 'LifeLab' as part of European Researchers Night 2018. Took part in the event presenting different exhibits to public audience, presenting the flow-sorting model and a Chip-seq model in the form of interactive games. |
Year(s) Of Engagement Activity | 2018 |
Description | Presenter and organising committee for RSSE exhibit "Race Against the Ageing Clock" |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Major exhibit at the Royal Society Summer Exhibition, also at Cambridge Science Fare and other events. Based on research from Reik lab and Babraham scientists on the discovery of mouse ageing clock. Involved scientists at all levels from Babraham discussing ageing research with scientifically engaged public. RSSE was attended by ~8000 people, and the Babraham Exhibit was popular and busy, resulting in numerous discussions of the ageing process and the potential for therapeutic approaches to ageing at all levels with members of the public. |
Year(s) Of Engagement Activity | 2018 |
URL | https://royalsociety.org/science-events-and-lectures/2018/summer-science-exhibition/exhibits/ageing-... |
Description | Race Against the Ageing Clock exhibit at Cambridge Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | 5 members of the lab were involved with the Race Against the Ageing Clock exhibit at the Cambridge Science Festival |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.sciencefestival.cam.ac.uk/ |
Description | Schools day (annual) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Visit by school children to do experiments in BI labs. All BI labs participate. |
Year(s) Of Engagement Activity | 2010,2011,2012,2013,2014,2015,2016 |