A genomic and chemogenomic approach to the protein quality control problem
Lead Research Organisation:
Royal Veterinary College
Department Name: Pathology and Pathogen Biology
Abstract
Strategic Research Priority: Bioscience for Health
Protein quality control is vital to cellular health. Defects in protein quality control underlie a broad range of diseases, and are closely linked to the ageing process. The aim of this study is to describe the processes that regulate and modulate protein quality control at a systems-level and to identify new chemical modulators. The project will combine the genetic tractability of the yeast micromammal Schizosaccharomyces pombe with mammalian cell biology and a vertebrate zebrafish model, providing a highly detailed understanding of the networks and pathways that regulate this process, and new tools for its study.
Protein quality control is vital to cellular health. Defects in protein quality control underlie a broad range of diseases, and are closely linked to the ageing process. The aim of this study is to describe the processes that regulate and modulate protein quality control at a systems-level and to identify new chemical modulators. The project will combine the genetic tractability of the yeast micromammal Schizosaccharomyces pombe with mammalian cell biology and a vertebrate zebrafish model, providing a highly detailed understanding of the networks and pathways that regulate this process, and new tools for its study.
Organisations
People |
ORCID iD |
| Claire Russell (Primary Supervisor) | |
| Christopher Minnis (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M009513/1 | 01/10/2015 | 31/03/2024 | |||
| 1632387 | Studentship | BB/M009513/1 | 01/10/2015 | 27/09/2019 | Christopher Minnis |
| Description | Our latest genetic analysis has now revealed in more detail the consequence of the most pathogenic mutation, the 1kb deletion. Taken together, our results imply that the minor 1-kb deletion transcript has three consequences for CLN3: to both lose and retain some inherent functions and to acquire abnormal characteristics. This has particular implications for the therapeutic development of juvenile CLN3 disease. |
| Exploitation Route | Data from this research has now be accepted for publication and will soon be online. Outcomes in this project are following on through another project as well as supporting several other avenues of research. In addition, data from this fundamental research has been the basis for another project grant. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology,Other |
| Description | International Society of Neurochemistry |
| Amount | £625 (GBP) |
| Organisation | International Society for Neurochemistry |
| Sector | Learned Society |
| Country | Switzerland |
| Start | 09/2018 |
| End | 09/2018 |
| Description | LIDo travel grant |
| Amount | £1,000 (GBP) |
| Organisation | University College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2016 |
| End | 10/2016 |
| Description | LIDo travel grant |
| Amount | £200 (GBP) |
| Organisation | University College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 09/2018 |
| End | 09/2018 |
| Description | NCL-Stiftung |
| Amount | £625 (GBP) |
| Organisation | NCL Foundation |
| Sector | Charity/Non Profit |
| Country | Germany |
| Start | 09/2018 |
| End | 09/2018 |
| Description | NCL-Stiftung |
| Amount | € 900 (EUR) |
| Organisation | NCL Foundation |
| Sector | Charity/Non Profit |
| Country | Germany |
| Start | 08/2017 |
| End | 08/2017 |
| Title | Synthetic Genetic Array for fission yeast btn1 mutant models |
| Description | Genetic interactions for Batten's disease in S. pombe mutant models. These include btn1-delta and mutations equivalent to the 1Kb deletions and the human missense mutation D416G named D363G in fission yeast. The data sets show both positive and negative interactions for each mutation which allows us to build up a genetic network to propose functionality of CLN3's orthologue btn1 and therefore infer. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | No |
| Impact | Genetically infers that the 1Kb deletion equivalent to the most come mutation has residual or a gain of function for btn1. |
| Description | BDFA lab openday |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | For charity donors and parent groups visited the Royal Veterinary College. I presented work from my project and demonstrated the zebrafish model with my principle-investigator of the project Claire Russell. It sparks questions and discussion. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.bdfa-uk.org.uk/laboratory-open-day-at-the-royal-veterinary-college/ |
| Description | NCL Boston 2016 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | Presented project proposal for this thesis in poster form, to everyone present at the international NCL conference in Boston. It was my first conference and a great start to a Ph.D. I learned a lot, got amazing feedback and enjoyed it thoroughly. It has generated good collaborations, discussion and networking for future work. |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://www.raredr.com/news/preview-ncl-2016 |
| Description | NCL London 2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | We had our international conference on NCL, where I was awarded the International Society of Neurochemistry grant to attend and gave a presentation on my model and findings thus far. It was a great experience and development, with lots of questions, debates and views exchanged. It was reported to be the most successful meeting thus far and has been leading big developments in the field. |
| Year(s) Of Engagement Activity | 2018 |
| URL | http://www.ncllondon2018.com |
| Description | NCL London 2018 -Stiftung |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | At NCL London 2018, we also had satellite meeting with other organisations such as NCL-Stiftung which had another meeting on the Juvenile form of NCL. I presented work from my thesis and lead to some interesting views and debates on to the funciton and implication of the data. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.ncl-stiftung.de |
| Description | NCL-Stiftung |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | In Hamburg, the jNCL Young Investigator Symposium took place, where we heard research from alot of international collaborators. I presented my own work to date on novel gentic markers and there was great dicussion and debate on the disease as well as its funciton throughout. It was a big impact as we were able to exchange knowledge and theories on our related subject as well as seen the impact on parent stories. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.ncl-stiftung.de/was-wir-machen/kooperationen/ |
| Description | UCL neuroscience symposium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Study participants or study members |
| Results and Impact | Presented a poster on my project, it was well recieved, sparking interesitng questions and dsicussions on similar neurodegenerative diseases. |
| Year(s) Of Engagement Activity | 2017,2018 |
| URL | https://www.ucl.ac.uk/research/domains/neuroscience/events/neuroscience-symposia |