Structural mechanisms of centriole assembly during cell duplication
Lead Research Organisation:
University of Oxford
Department Name: Biochemistry
Abstract
From embryo to adulthood and every day of our lives we rely on the normal growth and division of millions of cells. For each cell division our genetic material, packed in chromosomes, must also properly divide. In humans and animals this is achieved by an elaborate structure, called the nuclear spindle, organized by copies of the centrosome at each end of the cell. After division, each new cell has only one centrosome; therefore it must duplicate in order for further cell divisions to occur.
Centrosome duplication is a process for which we have relatively little information. We know that any abnormalities in this process can cause diseases or even cancer; however we do not know how this process is regulated, what is the role of each individual centrosomal component or how they assemble together. If we could understand how centrosome duplication takes place and how abnormalities can occur, then we could possibly devise treatments or new drugs. Therefore, there is much interest in understanding this process at the most detailed level possible.
We propose to use a combination of approaches, including cell biology, microscopy and biophysics to answer specific questions about the centrosome duplication process. We are interested in how their elaborate 9-fold symmetric shape is defined, and whether this is achieved by the same method in all organisms or whether there are significant differences. We would like to study how the cells control the start of the duplication process to ensure that it only happens once per cell division. Finally, we aim to find the correct place in the assembly for the various centrosomal components, similar to pieces in a puzzle.
The centrosome is a molecular machine, composed of many large proteins. To be able to study these components in sufficient detail, we first aim to find smaller, functional subunits, which we can analyze with biophysical tools. We can then make predictions for the properties of whole components based on these individual fragments, and test these predictions using electron microscopy and cell biology. Some important aspects of this work require expertise not present in our core group. Therefore we collaborate with internationally recognized groups in the UK and abroad to access the broadest base of expertise possible.
Centrosome duplication is a process for which we have relatively little information. We know that any abnormalities in this process can cause diseases or even cancer; however we do not know how this process is regulated, what is the role of each individual centrosomal component or how they assemble together. If we could understand how centrosome duplication takes place and how abnormalities can occur, then we could possibly devise treatments or new drugs. Therefore, there is much interest in understanding this process at the most detailed level possible.
We propose to use a combination of approaches, including cell biology, microscopy and biophysics to answer specific questions about the centrosome duplication process. We are interested in how their elaborate 9-fold symmetric shape is defined, and whether this is achieved by the same method in all organisms or whether there are significant differences. We would like to study how the cells control the start of the duplication process to ensure that it only happens once per cell division. Finally, we aim to find the correct place in the assembly for the various centrosomal components, similar to pieces in a puzzle.
The centrosome is a molecular machine, composed of many large proteins. To be able to study these components in sufficient detail, we first aim to find smaller, functional subunits, which we can analyze with biophysical tools. We can then make predictions for the properties of whole components based on these individual fragments, and test these predictions using electron microscopy and cell biology. Some important aspects of this work require expertise not present in our core group. Therefore we collaborate with internationally recognized groups in the UK and abroad to access the broadest base of expertise possible.
Technical Summary
Centrioles are structures in eukaryotic cells with almost universal 9-fold symmetry. They are large, typically 400 nm by 150 nm in size, and contain symmetric sets of microtubules. Centrioles serve primarily two roles: near the cell membrane they organize flagella and cilia, and in animal cells a pair of centrioles forms the centrosome, the primary microtubule organizing centre. To maintain their numbers centrioles must duplicate once per cell cycle. Defects in this process are linked to medical conditions such as ciliopathies, male sterility or even cancer. As a result, there is widespread interest in understanding how centrioles duplicate, how this process is controlled and what determines their unique architecture.
A relatively small number of proteins, including SAS-6, SAS-5 and SAS-4 in C. elegans and their equivalents in higher organisms, was identified by genetic analysis as critical for the initial steps of the duplication process. The most conserved member of this group, SAS-6, was recently studied by biophysical and cell biology methods, and shown to form oligomers similar to early ultrastructures in centriole duplication. Here, we propose to study how SAS-6 is regulated, how it interacts with other centriolar components, and how these complexes recruit microtubules to the growing centriole.
We plan to use a dissection approach, whereby centriolar components will be initially studied at the level of individual domains. We will use biophysical methods (CD, fluorescence, AUC and ITC) to characterize these domains and their interactions, and crystallography and NMR to obtain high-resolution structures. Information from individual components will be used to create models of higher-order assemblies, which will be studied through EM. The functional significance of complexes observed will then be examined in C. elegans embryos or human cell lines through residue substitutions designed to interfere with the assembly process.
A relatively small number of proteins, including SAS-6, SAS-5 and SAS-4 in C. elegans and their equivalents in higher organisms, was identified by genetic analysis as critical for the initial steps of the duplication process. The most conserved member of this group, SAS-6, was recently studied by biophysical and cell biology methods, and shown to form oligomers similar to early ultrastructures in centriole duplication. Here, we propose to study how SAS-6 is regulated, how it interacts with other centriolar components, and how these complexes recruit microtubules to the growing centriole.
We plan to use a dissection approach, whereby centriolar components will be initially studied at the level of individual domains. We will use biophysical methods (CD, fluorescence, AUC and ITC) to characterize these domains and their interactions, and crystallography and NMR to obtain high-resolution structures. Information from individual components will be used to create models of higher-order assemblies, which will be studied through EM. The functional significance of complexes observed will then be examined in C. elegans embryos or human cell lines through residue substitutions designed to interfere with the assembly process.
Planned Impact
We expect our activities to have societal and economic impact through three distinct pathways: direct relevance to medical conditions, education and training of people, and outreach into the community.
Centrioles are important for human cells as they organize flagella, cilia, and the mitotic spindle during cell division. Aberrations in centriole structure or numbers can affect human health in a number of ways. Abnormal cilia formation can disrupt cell migration during development, giving rise to genetic diseases collectively known as ciliopathies. This is an emerging class of multi-sympton conditions that can affect liver, kidneys, gut and the respiratory track. In adults, epithelial cells and sperm also use cilia and flagella for function, thus defects in centriole duplication can directly lead to male sterility or ectopic pregnancies. In addition, centrioles, in the guise of the centrosome, organize the mitotic spindle and are thus necessary for correct chromosome segregation across cell divisions.
Our current understanding of the origins of many of these conditions is limited, since our knowledge of centriole structure is incomplete. Our research aims to provide a mechanistic view of how centrioles are put together, what are the structural and functional roles of their components, and how they are regulated. Eventually, our research may yield diagnostics and tools to control centriole duplication and structure. We may achieve this kind of control in a not too-distant timeframe: already our work on the structural role of SAS-6 in centriole assembly suggests a possible avenue of inhibiting centriole duplication by limiting oligomerization of SAS-6.
In addition to long-term considerations, academic basic research provides benefits through education and training. The PDRAs involved in this project will be trained in new techniques that will enhance their skills. Our collaboration with cell biologists and electron microscopists, as well as the multi-disciplinary nature of the project ensures their exposure to new ideas. In addition, they will be mentored towards independence, by giving them the chance of designing as well as implementing research, by allowing self-management and by encouraging their exposure to large audiences through presentations and conferences. Whether they choose to remain in academia or move to industry, this course should allow them to assume leadership positions in the future.
The PI is also keen to recruit postgraduate and undergraduate students to participate in this project, and he and the PDRAs will provide appropriate personal training and mentoring. For students, this project can offer exposure to a wide range of experimental methods and a corresponding increase in skills. At the same time care will be taken that the students develop their ability to frame scientific questions and pursue answers with all tools available, as well as troubleshoot when problems arise. In collaboration with other departments, Oxford Biochemistry offers a number of Ph.D. studentships funded by BBSRC, EPSRC and the Wellcome Trust. Furthermore, the department requires undergraduate students to complete a 6-month research project at their final year. The PI is active in student recruitment from both of these pools.
Finally, we recognize that we have a responsibility to reach out to the community and explain our goals and prospects. We will engage in outreach activities, such as open days and scientific blogs, aimed at making our research accessible to the public, explaining why this research is important, how it can contribute to healthcare, and why they should support basic research.
Centrioles are important for human cells as they organize flagella, cilia, and the mitotic spindle during cell division. Aberrations in centriole structure or numbers can affect human health in a number of ways. Abnormal cilia formation can disrupt cell migration during development, giving rise to genetic diseases collectively known as ciliopathies. This is an emerging class of multi-sympton conditions that can affect liver, kidneys, gut and the respiratory track. In adults, epithelial cells and sperm also use cilia and flagella for function, thus defects in centriole duplication can directly lead to male sterility or ectopic pregnancies. In addition, centrioles, in the guise of the centrosome, organize the mitotic spindle and are thus necessary for correct chromosome segregation across cell divisions.
Our current understanding of the origins of many of these conditions is limited, since our knowledge of centriole structure is incomplete. Our research aims to provide a mechanistic view of how centrioles are put together, what are the structural and functional roles of their components, and how they are regulated. Eventually, our research may yield diagnostics and tools to control centriole duplication and structure. We may achieve this kind of control in a not too-distant timeframe: already our work on the structural role of SAS-6 in centriole assembly suggests a possible avenue of inhibiting centriole duplication by limiting oligomerization of SAS-6.
In addition to long-term considerations, academic basic research provides benefits through education and training. The PDRAs involved in this project will be trained in new techniques that will enhance their skills. Our collaboration with cell biologists and electron microscopists, as well as the multi-disciplinary nature of the project ensures their exposure to new ideas. In addition, they will be mentored towards independence, by giving them the chance of designing as well as implementing research, by allowing self-management and by encouraging their exposure to large audiences through presentations and conferences. Whether they choose to remain in academia or move to industry, this course should allow them to assume leadership positions in the future.
The PI is also keen to recruit postgraduate and undergraduate students to participate in this project, and he and the PDRAs will provide appropriate personal training and mentoring. For students, this project can offer exposure to a wide range of experimental methods and a corresponding increase in skills. At the same time care will be taken that the students develop their ability to frame scientific questions and pursue answers with all tools available, as well as troubleshoot when problems arise. In collaboration with other departments, Oxford Biochemistry offers a number of Ph.D. studentships funded by BBSRC, EPSRC and the Wellcome Trust. Furthermore, the department requires undergraduate students to complete a 6-month research project at their final year. The PI is active in student recruitment from both of these pools.
Finally, we recognize that we have a responsibility to reach out to the community and explain our goals and prospects. We will engage in outreach activities, such as open days and scientific blogs, aimed at making our research accessible to the public, explaining why this research is important, how it can contribute to healthcare, and why they should support basic research.
Organisations
- University of Oxford (Lead Research Organisation)
- Francis Crick Institute (Collaboration)
- Swiss Federal Institute of Technology in Lausanne (EPFL) (Collaboration)
- Paul Scherrer Institute (Collaboration)
- Swiss Tropical & Public Health Institute (Collaboration)
- Birkbeck, University of London (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- University of Würzburg (Collaboration)
Publications
Bianchi S
(2018)
Interaction between the Caenorhabditis elegans centriolar protein SAS-5 and microtubules facilitates organelle assembly.
in Molecular biology of the cell
Bonet R
(2013)
Characterization of 14-3-3-? Interactions with integrin tails.
in Journal of molecular biology
Busch J
(2017)
How to Break a Ring: Exploring the Mechanisms of SAS-6 Oligomerisation
in Biophysical Journal
Busch JMC
(2019)
A dynamically interacting flexible loop assists oligomerisation of the Caenorhabditis elegans centriolar protein SAS-6.
in Scientific reports
Cutts EE
(2015)
The centriolar protein CPAP G-box: an amyloid fibril in a single domain.
in Biochemical Society transactions
Erat MC
(2013)
Structural analysis of collagen type I interactions with human fibronectin reveals a cooperative binding mode.
in The Journal of biological chemistry
Hatzopoulos GN
(2013)
Structural analysis of the G-box domain of the microcephaly protein CPAP suggests a role in centriole architecture.
in Structure (London, England : 1993)
Hilbert M
(2013)
Caenorhabditis elegans centriolar protein SAS-6 forms a spiral that is consistent with imparting a ninefold symmetry
in Proceedings of the National Academy of Sciences
Description | Our research grant on studying the structural mechanisms of centriole assembly is now concluded. In the grant's first year we focused on C. elegans, a nematode worm that serves as model animal system in centriole studies. We addressed how C. elegans' centrioles differ from those of higher organisms; this information will prove critical when trying to compare experiments across C. elegans and other model systems. In year two we addressed how centriole elongate as a result of the protein CPAP, mutations of which lead to primary microcephaly. In the final year of the grant we returned to C. elegans centrioles, this time studying a protein seemingly unique to this class of organisms, SAS-5. We combined biophysical and biological information on SAS-5 to propose the first molecular mechanism of function. |
Exploitation Route | Our findings could inform academic research seeking to compare centriole across organisms. We have demonstrated significant variation in C. elegans, a model system, compared to vertebrates or algae. We have made a number of key predictions on centriolar organization, which could form the underlying hypotheses for further research. |
Sectors | Pharmaceuticals and Medical Biotechnology |
Description | Our work was primarily one of basic research, with major impact on the way we view centrioles from model organisms. However, at the same time the grant provided us with opportunities to engage with the wider public, and to train students and young scientists in cutting-edge methods. In particular, we note the training of two PhD students and three post-graduate researchers that took part in the work proposed. |
First Year Of Impact | 2013 |
Sector | Education |
Impact Types | Societal Economic |
Description | MRC grant of centriolar research (2016-19) |
Amount | £530,081 (GBP) |
Funding ID | MR/N009274/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2016 |
End | 06/2019 |
Description | Marie Sklodowska Curie Individual Fellowship |
Amount | £183,454 (GBP) |
Funding ID | 752069 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 06/2017 |
End | 06/2019 |
Title | Alpha4 Integrin Cytoplasmic Tail 1H and 15N Chemical Shift |
Description | Alpha4 Integrin Cytoplasmic Tail 1H and 15N Chemical Shift |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | Insight in cell adhesion complexes |
URL | http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=18718 |
Title | Beta2 Integrin Cytoplasmic Tail 1H and 15N Chemical Shift |
Description | Beta2 Integrin Cytoplasmic Tail 1H and 15N Chemical Shift |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | Insight in cell adhesion complexes |
URL | http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=18719 |
Title | Chemical shift assignments of PfEMP1 ATSCore - variant PFF0845c |
Description | Chemical shift assignments of PfEMP1 ATSCore - variant PFF0845c |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Insight into malaria virulence complex formation |
URL | http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=26772 |
Title | Chemical shift assignments of Spectrin repeat a17 |
Description | Chemical shift assignments of Spectrin repeat a17 |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Insight in formation of malaria virulence complex |
URL | http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=26773 |
Title | Chemical shifts for the N-terminal head group of ceSAS-6 |
Description | Chemical shifts for the N-terminal head group of ceSAS-6 |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | Insight in oligomerisation of SAS-6 centriolar protein |
URL | http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=18807 |
Title | Chemical shifts of the CPAP-interacting epitope of Danio rerio STIL |
Description | NMR chemical shifts of the CPAP-interacting epitope of Danio rerio STIL |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | Research publication |
URL | http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=19318 |
Title | Crystal structure of the RIM C2A domain from Drosophila |
Description | Structure of the D. melanogaster RIM synaptic protein C2A domain |
Type Of Material | Database/Collection of data |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | No impacts thus far |
URL | https://www.rcsb.org/structure/4TS6 |
Title | Crystallographic structure of 14-3-3-z in complex with integrin peptide |
Description | Crystallographic structure of 14-3-3-z in complex with integrin peptide |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | Insight in cell adhesion complexes |
URL | http://www.rcsb.org/structure/4HKC |
Title | Crystallographic structure of Drosophila RIM C2A domain |
Description | Crystallographic structure of Drosophila RIM C2A domain |
Type Of Material | Database/Collection of data |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | Insight in neuronal synapse function |
URL | http://www.rcsb.org/structure/4TS6 |
Title | Crystallographic structure of PFI1780w PHIST domain |
Description | Crystallographic structure of PFI1780w PHIST domain |
Type Of Material | Database/Collection of data |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Insight in erythrocyte modification by malaria parasite |
URL | http://www.rcsb.org/structure/4JLE |
Title | Crystallographic structure of human alpha spectrin domains 16-17 |
Description | Crystallographic structure of human spectrin alpha16-17 |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Insight on malaria virulence complex formation process |
URL | http://www.rcsb.org/structure/5J4O |
Title | Electron tomography - Detergent-insoluble skeleton of Plasmodium falciparum schizont |
Description | Electron tomography - Detergent-insoluble skeleton of Plasmodium falciparum schizont |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Insight in formation of malaria virulence complex |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-3123 |
Title | Electron tomography - Detergent-insoluble skeleton of Plasmodium falciparum schizont, labelled with anti-KAHRP antibody |
Description | Electron tomography - Detergent-insoluble skeleton of Plasmodium falciparum schizont, labelled with anti-KAHRP antibody |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Insight into formation of malaria virulence complex |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-3122 |
Title | Electron tomography - Detergent-insoluble skeleton of human erythrocyte |
Description | Electron tomography - Detergent-insoluble skeleton of human erythrocyte |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Insight into formation of malaria virulence complex |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-3117 |
Title | Electron tomography - Detergent-resistant skeleton of P. falciparum schizont |
Description | Electron tomography - Detergent-resistant skeleton of P. falciparum schizont |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Insight into formation of malaria virulence complex |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-3116 |
Title | NMR chemical shifts of C. elegans SAS-5 N-terminus |
Description | Sequence-specific NMR chemical shift assignments of the C. elegans SAS-5 N-terminal, microtubule-interacting domain |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Facilitated the characterisation of the SAS-5 / microtubule interaction |
URL | http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=27056 |
Title | Resonance assignments of the PHIST domain of P. falciparum protein PFI1780w |
Description | Resonance assignments of the PHIST domain of P. falciparum protein PFI1780w |
Type Of Material | Database/Collection of data |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Insight in erythrocyte modification by P. falciparum |
URL | http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=19719 |
Title | Sequence specific chemical shift assignments of the Caenorhabditis elegans SAS-6 N-terminal domain |
Description | Sequence specific chemical shift assignments of the Caenorhabditis elegans SAS-6 N-terminal domain |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | Insight in centriole formation process |
URL | http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=27607 |
Title | Sequence-specific resonance assignments of the Chlamydomonas reinhardtii SAS-6 N-terminal domain, F145E variant |
Description | NMR chemical shift assignment of the C. reinhardtii SAS-6 N-terminal domain |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | Datasets used for publication |
URL | https://bmrb.io/data_library/summary/index.php?bmrbId=50300 |
Title | Sequence-specific resonance assignments of the human SAS-6 F131D head domain |
Description | NMR chemical shift assignments of the human SAS-6 N-terminal domain |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | Dataset used in publication |
URL | https://bmrb.io/data_library/summary/index.php?bmrbId=50308 |
Title | Structure of C. elegans SAS-6 D123 variant |
Description | Crystallographic structure of an engineered variant of C. elegans SAS-6 N-terminal domain |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | No non-academic impact |
URL | http://www.rcsb.org/pdb/explore/explore.do?structureId=4G79 |
Title | Structure of a stabilised C. elegans SAS-6 N-terminal dimer |
Description | Crystallographic structure of a stabilised dimer formed by the C. elegans SAS-6 N-terminal domain |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | No non-academic impact |
URL | http://www.rcsb.org/pdb/explore/explore.do?structureId=4GEU |
Title | Structure of a stabilised C. elegans SAS-6 N-terminal dimer, second form |
Description | Crystallographic structure of a stabilised C. elegans SAS-6 dimer, second crystal form |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | No non-academic impact |
URL | http://www.rcsb.org/pdb/explore/explore.do?structureId=4GEX |
Title | Structure of the C. elegans SAS-5 Implico dimerization domain |
Description | Crystallographic structure of the C. elegans SAS-5 Implico dimerization domain |
Type Of Material | Database/Collection of data |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | No non-academic impacts |
URL | http://www.rcsb.org/pdb/explore/explore.do?structureId=4YNH |
Title | Structure of the C. elegans SAS-5 coiled coil domain |
Description | Crystallographic structure of the C. elegans SAS-5 coiled coil domain |
Type Of Material | Database/Collection of data |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | No non-academic impacts |
URL | http://www.rcsb.org/pdb/explore/explore.do?structureId=4YV4 |
Title | Structure of the Plasmodium falciparum SIP2 DNA-binding AP2 tandem repeat in complex with two SPE2 half-sites |
Description | Crystal structure of the P. falciparum SIP2 transcription factor in complex with DNA |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | No impacts thus far |
URL | https://www.rcsb.org/structure/6SY0 |
Title | Structure of the coiled-coil dimer of C. elegans SAS-6 |
Description | Crystallographic structure of a C. elegans SAS-6 dimer mediated by the coiled coil |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | No non-academic impact |
URL | http://www.rcsb.org/pdb/explore/explore.do?structureId=4GFA |
Title | Structure of the coiled-coil dimer of C. elegans SAS-6, second form |
Description | Crystallographic structure of a C. elegans SAS-6 dimer mediated by the coiled coil, second form |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | No non-academic impact |
URL | http://www.rcsb.org/pdb/explore/explore.do?structureId=4GFC |
Title | Structure of the human SAS-6 N-terminal domain, F131E mutant |
Description | Crystal structure of the human SAS-6 head domain |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | Dataset used in publication |
URL | https://www.rcsb.org/structure/6Z4A |
Title | Structure of the zebrafish CPAP G-box |
Description | Crystallographic structure of the zebrafish CPAP G-box domain |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | No non-academic impact |
URL | http://www.rcsb.org/pdb/explore/explore.do?structureId=4LZF |
Title | Structure of the zebrafish CPAP G-box in complex with STIL |
Description | Crystallographic structure of a complex between the zebrafish proteins CPAP and STIL |
Type Of Material | Database/Collection of data |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | No non-academic impact |
URL | http://www.rcsb.org/pdb/explore/explore.do?structureId=4LD3 |
Description | Oxford - Birkbeck - Crick collaboration |
Organisation | Birkbeck, University of London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Biophysical insight on interactions of malaria parasite proteins. |
Collaborator Contribution | Electron microscopy (Birkbeck - Prof. Saibil) and in cellulo (Crick - Dr. Blackman) assays in support of our biophysical insights. |
Impact | Joint research publication with Saibil and Blackman groups. |
Start Year | 2013 |
Description | Oxford - Birkbeck - Crick collaboration |
Organisation | Francis Crick Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Biophysical insight on interactions of malaria parasite proteins. |
Collaborator Contribution | Electron microscopy (Birkbeck - Prof. Saibil) and in cellulo (Crick - Dr. Blackman) assays in support of our biophysical insights. |
Impact | Joint research publication with Saibil and Blackman groups. |
Start Year | 2013 |
Description | Oxford - EPFL collaboration |
Organisation | Swiss Federal Institute of Technology in Lausanne (EPFL) |
Country | Switzerland |
Sector | Public |
PI Contribution | We have developed a collaboration with a group at the EPFL, Switzerland, to evaluate structural insights in cellular systems. |
Collaborator Contribution | In vivo and in cellulo assays in support of structural insights gained for centriolar proteins. |
Impact | Joint research publications with Prof. Gonczy |
Start Year | 2010 |
Description | Oxford - LMB collaboration |
Organisation | University of Cambridge |
Department | Department of Genetics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provision of recombinant protein samples from our laboratory to that of Prof. David Glover. Sharing of unpublished information on centriolar protein structure. |
Collaborator Contribution | Sharing of unpublished information on centriolar protein interactions. Provision of genetic constructs for our laboratory. |
Impact | No outputs to date. Multidisciplinary collaboration between structural biology and biophysics (our group) and cell biologists (Prof. Glover). |
Start Year | 2017 |
Description | Oxford - SwissTPH collaboration |
Organisation | Swiss Tropical & Public Health Institute |
Country | Switzerland |
Sector | Academic/University |
PI Contribution | Provide structural insights in the role of malaria parasite proteins. |
Collaborator Contribution | In cellulo assays to test our structural insights. Work performed with Profs. Beck and Voss. |
Impact | Joint research publications with Prof. Beck. |
Start Year | 2011 |
Description | Oxford - Wurzburg collaboration |
Organisation | University of Wurzburg |
Country | Germany |
Sector | Academic/University |
PI Contribution | Structural insights on role of neuronal synapse proteins. |
Collaborator Contribution | Electrophysiology and in vivo assays testing our structural insights. Work with (formerly) Prof. Langenhan and (currently) Prof. Heckmann. |
Impact | No published outputs yet. |
Start Year | 2012 |
Description | Oxford-PSI collaboration |
Organisation | Paul Scherrer Institute |
Country | Switzerland |
Sector | Academic/University |
PI Contribution | Collaboration with a group at the Paul Scherrer Institut, Switzerland, for electron microscopy |
Collaborator Contribution | EM and in cellulo studies of microtubule binding in support of structural insights from centriolar proteins. |
Impact | Joint research publications with group of Prof. Steinmetz |
Start Year | 2010 |
Description | Oxford Open Days |
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 | Public/other audiences |
Results and Impact | Open Days in Oxford Biochemistry, targeting prospective undergraduate students as well as their parents. The Open Days feature a mixture of face-to-face meetings, research demos, and organised talks. |
Year(s) Of Engagement Activity | 2013,2014,2015,2016,2017,2018,2019 |
Description | Research talk to prospective DPhil students |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Research talks to prospective structural biology DPhil students to inform their decisions on which research topic(s) to devote their studies on. Two students decided to do their PhDs on centriole biology. |
Year(s) Of Engagement Activity | 2012,2013,2014,2015 |
Description | School outreach |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Presentation of research demos to 30-60 primary school children. The children were engaged directly by asking them to participate (i.e. perform) some simple chemistry experiments. |
Year(s) Of Engagement Activity | 2017,2018 |
Description | Talk at Biochemical Society meeting; Repetitive, Non-Globular Proteins: Nature to Nanotechnology (York 30/03/2015-01/04/2015) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Talk initiated many discussions and prompted the publication of our results No realisable impact |
Year(s) Of Engagement Activity | 2015 |
URL | https://www.biochemistry.org/Events/tabid/379/View/Programme/MeetingNo/SA168/Default.aspx |
Description | Talk at ETH Zurich |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Talk on centriolar research at the ETH Zurich, Switzerland |
Year(s) Of Engagement Activity | 2016 |
Description | Talk at UCL - Birbeck |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Talk on centriolar research at UCL / Birbeck, London |
Year(s) Of Engagement Activity | 2016 |
Description | Talk at University of Edinburgh |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Talk on centriolar research at the University of Edinburgh |
Year(s) Of Engagement Activity | 2016 |
Description | Talk at the Australian National University |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Talk on centriolar research at the Australian National University, Canberra |
Year(s) Of Engagement Activity | 2016 |
Description | Talk at the SEE-DRUG 2015 conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Invited presentation at the 2015 SEE-DRUG conference, Patras, Greece, June 17-20 2015 |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.seedrug.upatras.gr/index.php?option=com_content&view=article&id=104&Itemid=221 |
Description | Talk at the Structural Biology 2017 conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Invited presentation at the Structural Biology 2017 conference in Zurich, Switzerland, Sept. 18-20 2017 |
Year(s) Of Engagement Activity | 2017 |
URL | https://structuralbiology.conferenceseries.com/2017/ |
Description | Talk at the University of Wurzburg |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Participants in your research or patient groups |
Results and Impact | Invited seminar at the Institute of Physiology of the University of Wurzburg (Germany) on 28/01/2013. Title: "Structural basis of centriolar 9-fold symmetry" no actual impacts realised to date |
Year(s) Of Engagement Activity | 2013 |
Description | Talk at the University of Wurzburg |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Invited presentation at the University of Wurzburg on Dec. 1st 2015 |
Year(s) Of Engagement Activity | 2015 |
Description | Undergraduate research presentations |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Undergraduate students |
Results and Impact | Recruited two undergraduate students to work on this project Helped undergraduate students decide what research to pursue as part of their Biochemistry degree. |
Year(s) Of Engagement Activity | 2012,2013,2014,2015,2016,2017,2018,2019 |