Cytochrome c oxidase: structure, function and malfunction
Lead Research Organisation:
Birkbeck, University of London
Department Name: Biological Sciences
Abstract
To live we need a permanent supply of energy. This is provided to our cells by a cascade of reactions that breaks down the food we eat into a universal fuel: the ATP. This process mainly occurs in organelles called mitochondria and is known as cellular respiration. The main machinery that mitochondria use to produce ATP is the respiratory chain. It is composed of four complexes, embedded in the mitochondrial inner membrane, that work together to build up an electrochemical gradient called the proton motive force and which drives ATP synthesis. Most of this gradient is in the form of protons which are pumped across the inner mitochondrial membrane by the respiratory chain complexes.
An increasing number of human pathologies are associated with defects in components of the respiratory chain. In many instances, this is because the malfunction has a direct impact on their primary role in energy production via the proton gradient that they form, or because it leads to an increased production of damaging free radicals. Cytochrome c oxidase (CcO) is the terminal enzyme of our respiratory chain. It transforms the oxygen we breathe into water and greatly contributes to the generation of the proton gradient. Alterations (or mutations) in its structure have been linked with diverse pathologies such as myopathy, therapy-resistant epilepsy, neurological diseases and prostate cancer.
Although the overall chemistry of mitochondrial CcO is fairly well understood, it has proven much more difficult to determine how this produces the essential proton gradient. Various hypotheses were formulated based on the available structures of the enzyme (of which only one is of mitochondrial origin, in this case bovine), but were challenged by mutagenesis work performed on smaller bacterial homologues. Today it appears that the major drawback in understanding the mechanism of mitochondrial CcO, and the effects of human disease-related mutations in particular, is the lack of a system to generate large amounts of purified protein containing defined point mutations.
Remarkably, the CcO that is present in Baker's yeast mitochondria is almost identical to that in human mitochondria. The nuclear and mitochondrial DNAs which encode CcO are both amenable to mutagenesis so alterations can be made in any part of the CcO structure to investigate its function. We have thus engineered a yeast system to allow large-scale production of mutants and will use it to address fundamental questions relative to human mitochondrial CcOs.
At first, we will identify the route taken by the protons to cross the protein structure by measuring CcO's ability to pump protons after alterations have been made in chosen area. We will then use advanced techniques like infrared spectroscopy to look at the concerted movement of atoms within CcO's structure and bring experimental evidences of the mechanism following which protons are being pumped. This should tell us more about the principles that govern and control the complex activity and will be our starting point to investigate how factors or signals external to the reaction centre can, in vivo, regulate CcO's activity. This will be of particular interest to understand how the human CcO has adapted to different energy requirements depending on tissue type. We will aim to obtain a detailed 3D structure of the yeast CcO to confirm our hypotheses. As we unravel the details of CcO's action, we will introduce identified human disease-related mutations in our yeast system in order to investigate the nature of their malfunction. Finally, we will aim at progressively incorporating the human genes or parts of the human enzyme in our yeast system. This will create as even better model for the study of human diseases and the development and testing of new therapies.
An increasing number of human pathologies are associated with defects in components of the respiratory chain. In many instances, this is because the malfunction has a direct impact on their primary role in energy production via the proton gradient that they form, or because it leads to an increased production of damaging free radicals. Cytochrome c oxidase (CcO) is the terminal enzyme of our respiratory chain. It transforms the oxygen we breathe into water and greatly contributes to the generation of the proton gradient. Alterations (or mutations) in its structure have been linked with diverse pathologies such as myopathy, therapy-resistant epilepsy, neurological diseases and prostate cancer.
Although the overall chemistry of mitochondrial CcO is fairly well understood, it has proven much more difficult to determine how this produces the essential proton gradient. Various hypotheses were formulated based on the available structures of the enzyme (of which only one is of mitochondrial origin, in this case bovine), but were challenged by mutagenesis work performed on smaller bacterial homologues. Today it appears that the major drawback in understanding the mechanism of mitochondrial CcO, and the effects of human disease-related mutations in particular, is the lack of a system to generate large amounts of purified protein containing defined point mutations.
Remarkably, the CcO that is present in Baker's yeast mitochondria is almost identical to that in human mitochondria. The nuclear and mitochondrial DNAs which encode CcO are both amenable to mutagenesis so alterations can be made in any part of the CcO structure to investigate its function. We have thus engineered a yeast system to allow large-scale production of mutants and will use it to address fundamental questions relative to human mitochondrial CcOs.
At first, we will identify the route taken by the protons to cross the protein structure by measuring CcO's ability to pump protons after alterations have been made in chosen area. We will then use advanced techniques like infrared spectroscopy to look at the concerted movement of atoms within CcO's structure and bring experimental evidences of the mechanism following which protons are being pumped. This should tell us more about the principles that govern and control the complex activity and will be our starting point to investigate how factors or signals external to the reaction centre can, in vivo, regulate CcO's activity. This will be of particular interest to understand how the human CcO has adapted to different energy requirements depending on tissue type. We will aim to obtain a detailed 3D structure of the yeast CcO to confirm our hypotheses. As we unravel the details of CcO's action, we will introduce identified human disease-related mutations in our yeast system in order to investigate the nature of their malfunction. Finally, we will aim at progressively incorporating the human genes or parts of the human enzyme in our yeast system. This will create as even better model for the study of human diseases and the development and testing of new therapies.
Technical Summary
The aim of this project is to elucidate the pumping mechanism of CcO and to investigate the effect of allosteric factors and isoforms on catalysis, using, for the first time, a yeast system that allows production and large scale purification of mitochondrial mutant forms of the enzyme. We will also start developing yeast as a platform for the construction of a chimeric yeast/human CcO.
Initial focus will be put on identifying the internal hydrophilic pathway responsible for proton pumping. This will involve accurate measurements of ADP/Oxygen ratios on preparations of intact mitochondria from mutant strains.
We will then address the coupling mechanism using time-resolved FTIR spectroscopy to detect concerted movements of key amino acids and water molecules on chosen reaction steps with the purified CcO. This will be done on photolysis of the fully reduced CO-bound enzyme, comparing the signals recorded for the wild-type and mutant forms and, subsequently, be extended to redox reactions.
We will investigate how long range factors can regulate catalysis. For instance, we will follow by FTIR spectroscopy the structural changes induced by the binding of ADP or ATP to allosteric sites on yeast supernumerary subunits. This will include the design of a range of mutants to mimic post-translational modifications such as phosphorylation.
We will aim to crystallise the yeast CcO and resolve its 3D X-ray structure.
Finally, we will use our yeast system to investigate the effect of human disease-related mutations in CcO. We will use a range of biochemical methods to determine level of expression/stability, turnover number, affinity for its substrate, ability to pump proton and at which stoichiometry. If required, more advanced biophysical techniques including FTIR spectroscopy and fast kinetics recording will be used. Ultimately, as the project develops, we will look at the effect of such alterations on a chimeric yeast/human enzyme.
Initial focus will be put on identifying the internal hydrophilic pathway responsible for proton pumping. This will involve accurate measurements of ADP/Oxygen ratios on preparations of intact mitochondria from mutant strains.
We will then address the coupling mechanism using time-resolved FTIR spectroscopy to detect concerted movements of key amino acids and water molecules on chosen reaction steps with the purified CcO. This will be done on photolysis of the fully reduced CO-bound enzyme, comparing the signals recorded for the wild-type and mutant forms and, subsequently, be extended to redox reactions.
We will investigate how long range factors can regulate catalysis. For instance, we will follow by FTIR spectroscopy the structural changes induced by the binding of ADP or ATP to allosteric sites on yeast supernumerary subunits. This will include the design of a range of mutants to mimic post-translational modifications such as phosphorylation.
We will aim to crystallise the yeast CcO and resolve its 3D X-ray structure.
Finally, we will use our yeast system to investigate the effect of human disease-related mutations in CcO. We will use a range of biochemical methods to determine level of expression/stability, turnover number, affinity for its substrate, ability to pump proton and at which stoichiometry. If required, more advanced biophysical techniques including FTIR spectroscopy and fast kinetics recording will be used. Ultimately, as the project develops, we will look at the effect of such alterations on a chimeric yeast/human enzyme.
Planned Impact
Who will benefit from this research?
-researchers in biological electron transfer and energy coupling;
-UK and worldwide Research Centres (e.g. the Mitochondrial Biology Unit in Cambridge, The Mitochondrial Centre, Newcastle, the Mitochondrial Research & Innovation Group, Rochester, USA) and medical charities and public domain sites (e.g. The United Mitochondrial Disease Foundation) devoted to mitochondrial research and its wider implications;
-members of the EU COST Action CM1306 (Understanding Movement and Mechanism in Molecular Machines) whose main objective is to improve understanding of the dynamics of protein complexes on catalysis by bridging neighbouring scientific fields and fostering applicative outcomes;
-patients and families of patients affected by CcO-related mitochondrial diseases.
How will they benefit from this research?
Basic researchers in related areas will benefit from the mechanistic understanding and structures important for energy coupling that should find applicability in other biological redox systems. Moreover, if the behaviour of yeast mutants is as predicted, a common picture for all forms of CcO will have been established, providing a resolution of current CcO mechanism controversies.
Members of the more diverse organisations above will be particularly interested in our development of this yeast CcO system as a platform for understanding mechanism and control of human mitochondrial CcO function and its malfunction in diseases. This yeast system will provide the only currently viable genetic system to test effects of known mutations of human mitochondrial CcO, using an enzyme that closely resembles its structure in all key aspects. Its extension into a system that assembles a chimeric yeast/human enzyme will also be of great benefit for patients as it can be used for the development and testing of new therapies.
Timescales. Within the timeframe of the project, we will bring new experimental evidences of the coupling mechanism, establish the function of the H channel region of mitochondrial forms of CcO and provide insights into how such enzymes are modulated by environmental factors. This yeast system is already usable to test effects of known human CcO mutations that have been linked to disease states. We will work closely with our clinical collaborator Dr Rahman, involved in collecting such mutational/clinical data to gain a mechanistic understanding of their malfunction. During this project lifetime, and in collaboration with Dr Meunier, we will extend the technology and expertise specifically to create a chimeric yeast/human system. On a longer term, this should lead to a viable platform for the detailed characterisation of the mechanisms underlying CcO-related human pathologies.
Staff development. The PDRA involved in the project will gain expertise with a wide range of biochemical and advanced biophysical methods. Through our collaborations with other laboratories in London (Peter Rich, respiratory complexes), France (Brigitte Meunier, genetics) and Cambridge (Leo Sazanov, crystallography) they will gain additional skills. Through my participation in EU COST Action, funds will be available for exchange between laboratories and myself and the PDRA will apply for COST-funded 'Short Term Scientific Missions' to learn expertise of our collaborators and in particular with the group of Peter Brzezinski (Sweden). The research skills that will be gained during this project are applicable to other major enzymes, including several of medical interest. In addition, professional skills that staff will develop will be applicable in other employment sectors for example ability to multi-task, work in a team and communicate with scientists and non-scientists. Hence, the project will provide skills for onward employment and career development.
-researchers in biological electron transfer and energy coupling;
-UK and worldwide Research Centres (e.g. the Mitochondrial Biology Unit in Cambridge, The Mitochondrial Centre, Newcastle, the Mitochondrial Research & Innovation Group, Rochester, USA) and medical charities and public domain sites (e.g. The United Mitochondrial Disease Foundation) devoted to mitochondrial research and its wider implications;
-members of the EU COST Action CM1306 (Understanding Movement and Mechanism in Molecular Machines) whose main objective is to improve understanding of the dynamics of protein complexes on catalysis by bridging neighbouring scientific fields and fostering applicative outcomes;
-patients and families of patients affected by CcO-related mitochondrial diseases.
How will they benefit from this research?
Basic researchers in related areas will benefit from the mechanistic understanding and structures important for energy coupling that should find applicability in other biological redox systems. Moreover, if the behaviour of yeast mutants is as predicted, a common picture for all forms of CcO will have been established, providing a resolution of current CcO mechanism controversies.
Members of the more diverse organisations above will be particularly interested in our development of this yeast CcO system as a platform for understanding mechanism and control of human mitochondrial CcO function and its malfunction in diseases. This yeast system will provide the only currently viable genetic system to test effects of known mutations of human mitochondrial CcO, using an enzyme that closely resembles its structure in all key aspects. Its extension into a system that assembles a chimeric yeast/human enzyme will also be of great benefit for patients as it can be used for the development and testing of new therapies.
Timescales. Within the timeframe of the project, we will bring new experimental evidences of the coupling mechanism, establish the function of the H channel region of mitochondrial forms of CcO and provide insights into how such enzymes are modulated by environmental factors. This yeast system is already usable to test effects of known human CcO mutations that have been linked to disease states. We will work closely with our clinical collaborator Dr Rahman, involved in collecting such mutational/clinical data to gain a mechanistic understanding of their malfunction. During this project lifetime, and in collaboration with Dr Meunier, we will extend the technology and expertise specifically to create a chimeric yeast/human system. On a longer term, this should lead to a viable platform for the detailed characterisation of the mechanisms underlying CcO-related human pathologies.
Staff development. The PDRA involved in the project will gain expertise with a wide range of biochemical and advanced biophysical methods. Through our collaborations with other laboratories in London (Peter Rich, respiratory complexes), France (Brigitte Meunier, genetics) and Cambridge (Leo Sazanov, crystallography) they will gain additional skills. Through my participation in EU COST Action, funds will be available for exchange between laboratories and myself and the PDRA will apply for COST-funded 'Short Term Scientific Missions' to learn expertise of our collaborators and in particular with the group of Peter Brzezinski (Sweden). The research skills that will be gained during this project are applicable to other major enzymes, including several of medical interest. In addition, professional skills that staff will develop will be applicable in other employment sectors for example ability to multi-task, work in a team and communicate with scientists and non-scientists. Hence, the project will provide skills for onward employment and career development.
Organisations
- Birkbeck, University of London (Lead Research Organisation)
- Institute for Integrative Biology of the Cell (I2BC) (Collaboration)
- University College London (Collaboration)
- Stockholm University (Collaboration)
- Institute of Science and Technology Austria (Collaboration)
- Medical Research Council (Project Partner)
- University College London (Fellow, Project Partner)
- French National Centre for Scientific Research (Project Partner)
Publications
Björck ML
(2019)
Proton-transfer pathways in the mitochondrial S. cerevisiae cytochrome c oxidase.
in Scientific reports
Hartley AM
(2019)
Structure of yeast cytochrome c oxidase in a supercomplex with cytochrome bc1.
in Nature structural & molecular biology
Hartley AM
(2020)
Rcf2 revealed in cryo-EM structures of hypoxic isoforms of mature mitochondrial III-IV supercomplexes.
in Proceedings of the National Academy of Sciences of the United States of America
Ing G
(2022)
Cryo-EM structure of a monomeric yeast S. cerevisiae complex IV isolated with maltosides: Implications in supercomplex formation.
in Biochimica et biophysica acta. Bioenergetics
Jordan SF
(2019)
Promotion of protocell self-assembly from mixed amphiphiles at the origin of life.
in Nature ecology & evolution
Jordan SF
(2021)
Spontaneous assembly of redox-active iron-sulfur clusters at low concentrations of cysteine.
in Nature communications
Liu C
(2018)
Phosphonomethyl Oligonucleotides as Backbone-Modified Artificial Genetic Polymers.
in Journal of the American Chemical Society
Maréchal A
(2018)
Comparison of redox and ligand binding behaviour of yeast and bovine cytochrome c oxidases using FTIR spectroscopy.
in Biochimica et biophysica acta. Bioenergetics
Maréchal A
(2020)
A common coupling mechanism for A-type heme-copper oxidases from bacteria to mitochondria.
in Proceedings of the National Academy of Sciences of the United States of America
Mühleip A
(2023)
Structural basis of mitochondrial membrane bending by the I-II-III2-IV2 supercomplex.
in Nature
Description | Birkbeck / Wellcome Trust Institutional Strategic Support Fund (ISSF) |
Amount | £24,971 (GBP) |
Organisation | Birkbeck, University of London |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2018 |
End | 10/2018 |
Description | Birkbeck / Wellcome Trust Institutional Strategic Support Fund (ISSF) |
Amount | £22,917 (GBP) |
Organisation | Birkbeck, University of London |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2015 |
End | 05/2017 |
Description | Royal Society Research Grants Scheme |
Amount | £15,000 (GBP) |
Funding ID | RG150631 |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2016 |
End | 03/2017 |
Title | Deposition of 1 electron microscopy map into the Electron Microscopy Data Base EMD-14436 |
Description | Cryo-EM map has been deposited in the Electron Microscopy Data Bank under accession no. EMD-14436 for a monomeric respiratory complex IV isolated from S. cerevisiae with maltosides |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | The coordinates of the atomic model of the monomeric CIV built from this EM map have been deposited in the Protein Data Bank under PDB ID code 1Z10 |
URL | https://www.ebi.ac.uk/emdb/EMD-14436 |
Title | Deposition of 1 entry to the Protein Data Bank 6HU9 |
Description | This entry to the Protein Data Bank provides atomic details of the structure of yeast mitochondrial cytochrome c oxidase in a supercomplex with cytochrome bc1 in the biologically relevant 2:2 stoechiometry. |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Saccharomyces cerevisiae is the ideal model system universally used to test/verify hypothesis in the study of mitochondrial respiratory chains. This model will permit the validation of past and future mutagenesis studies and will stand as a reference across disciplines for the advancement of knowledge. |
URL | https://www.ebi.ac.uk/pdbe/entry/pdb/6hu9 |
Title | Deposition of 1 entry to the Protein Data Bank ID 1Z10 |
Description | This entry to the Protein Data Bank provides atomic details of the structure of a monomeric yeast mitochondrial cytochrome c oxidase isolated from S. cerevisiae with maltosides |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | This work provides insight on the role of protein:protein interaction (and in particular Cox5) for the association of respiratory complex IV with complex III to form the yeast supercomplex |
URL | https://www.rcsb.org/structure/7Z10 |
Title | Deposition of 2 entries to the Protein Data Bank 6T15 and 6T0B |
Description | These entries to the Protein Data Bank provide atomic details of the structure of the 2:1 and 2:2, respectively, hypoxic yeast mitochondrial supercomplex formed by cytochrome bc1 and cytochrome c oxidase. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | Saccharomyces cerevisiae is the ideal model system universally used to test/verify hypothesis in the study of mitochondrial respiratory chains. This is the frist setof structure reporting atomic details of respiratory expression isoforms. They permit validation of past and future mutagenesis studies and will stand as a reference across disciplines for the advancement of knowledge. |
URL | https://www.rcsb.org/structure/6t15 |
Title | Deposition of 3 electron microscopy maps into the Electron Microscopy Data Base EMD-0262, EMD-0268, EMD-0269 |
Description | These three EM maps are the result of extensive image processing which led to the structure, at atomic resolution, of the supercomplex formed by mitochondrial complexes IV and III |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Together, these maps allowed the construction of the first atomic model of a mitochondrial III-IV supercomplex (deposited in the PDB as 6HU9) |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-0262/index |
Title | Deposition of 7 electron microscopy maps into the Electron Microscopy Data Base EMD-0262, EMD-0268, EMD-0269 |
Description | Cryo-EM maps have been deposited in the Electron Microscopy Data Bank under accession nos. EMD-10317 (CIII2) and EMD-10318 (CIV5B) for ?rox1; EMD-10340 (III2IV5B2 SC), EMD-10335 (CIV5B-a), and EMD-10334 (CIV5B-b) for cox5ab; and EMD-10375 (CIV5A-a) and EMD-10376 (CIV5A-b) for ?cox5b. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | The coordinates of the atomic models of the CIV5B-containing SCs built from a combination of these seven EM maps have been deposited in the Protein Data Bank under PDB ID codes 6T15 (?rox1 III2IV5B1) and 6T0B (cox5ab III2IV5B2). |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-10318 |
Description | Crystallisation and structure determination of cytochrome c oxidase from Saccharomyces cerevisiae |
Organisation | Institute of Science and Technology Austria |
Country | Austria |
Sector | Academic/University |
PI Contribution | We send them samples of cytochrome c oxidase purified to crystallisation quality from yeast S. cerevisiae and setup crystallisation trials on the fresh preparations under their guidance. |
Collaborator Contribution | They guide us to improve the stability/purity of our protein preparation and perform extensive crystallisation screens on frozen samples of the enzyme. |
Impact | At today no output or outcome can be reported. Disciplines involved: Biochemistry, Biophysics. |
Start Year | 2015 |
Description | Effect of mutations in cytochrome c oxidase from Saccharomyces cerevisiae |
Organisation | Institute for Integrative Biology of the Cell (I2BC) |
Country | France |
Sector | Academic/University |
PI Contribution | We study and analyse usign a combination of biochemistry and biophysics methods the effect of point mutations on the catalytic activity of cytochrome c oxidase. |
Collaborator Contribution | They provide us with strains of yeast S. cerevisae containing mutation in their cytochrome c oxidase (both nuclear and mitochondrial-DNA encoded subunits) to test/verify hypothesis. |
Impact | Several publications since 2012. Disciplines involved: genetics, biochemistry, biophysics. |
Start Year | 2012 |
Description | Effect of point mutations and isoform on the kinetics of the reaction of yeast cytochrome c oxidase with dioxygen |
Organisation | Stockholm University |
Department | Department of Biochemistry and Biophysics |
Country | Sweden |
Sector | Academic/University |
PI Contribution | We have identified the mutant strains of interest from their level of oxidase expression, UV visible absorption signature and rate of oxygen consumption in comparison with WT. These are point mutations of I67N, N99D in subunit I and the constructs of the two natural isoforms of the yeast oxidase where only COX5A or 5B is expressed. We then grow the cells and make mitochondrial membrane preparations of the selected mutant oxidase or purify it. This material is then used for the flow-flash experiments in Stockholm. |
Collaborator Contribution | They have the specialist flow-flash apparatus that permits fast kinetics measurements on reaction of the four or two electron-reduced WT and mutant forms (or isoforms) of oxidase with molecular oxygen. They can also measure proton uptake by the enzyme on selected catalytic steps. |
Impact | Exchange of knowledge, training of PhD students and PDRA. Disciplines involved: biophysics, biochemistry, molecular biology. Publication: Proton-transfer pathways in the mitochondrial S. cerevisiae cytochrome c oxidase. Björck ML, Vilhjálmsdóttir J, Hartley AM, Meunier B, Näsvik Öjemyr L, Maréchal A, Brzezinski P. Sci Rep. 2019 Dec 27;9(1):20207. doi: 10.1038/s41598-019-56648-9. PMID: 31882860 |
Start Year | 2016 |
Description | Mitochondrial respiratory supercomplexes, structure and function with the group of Alexey Amunts |
Organisation | Stockholm University |
Country | Sweden |
Sector | Academic/University |
PI Contribution | we provided expertise in respiratory complexes and supercomplexes including functional characterisation |
Collaborator Contribution | they isolated and solved atomic structures of new respiratory supercomplexes |
Impact | Publication in Nature in 2023 (DOI: 10.1038/s41586-023-05817-y) |
Start Year | 2022 |
Description | Origin of Life |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We provide expertise in redox processes and protein biochemistry/chemistry as well as access and support to advanced spectroscopy techniques (including infrared and UV vis) and cryoEM. We train postdoc and PhD students on specialist instruments in our lab. |
Collaborator Contribution | They provide expertise in the field of origin of life, postdoc and PhD students to carry out the work. |
Impact | Publications: Promotion of protocell self-assembly from mixed amphiphiles at the origin of life. Jordan SF, Rammu H, Zheludev IN, Hartley AM, Maréchal A, Lane N. Nat Ecol Evol. 2019 Dec;3(12):1705-1714. doi: 10.1038/s41559-019-1015-y. Epub 2019 Nov 4. PMID: 31686020 Spontaneous assembly of redox-active iron-sulfur clusters at low concentrations of cysteine. Jordan SF, Ioannou I, Rammu H, Halpern A, Bogart LK, Ahn M, Vasiliadou R, Christodoulou J, Maréchal A, Lane N. Nat Commun. 2021 Oct 11;12(1):5925. doi: 10.1038/s41467-021-26158-2. PMID: 34635654 Funding: BBSRC sLoLa grant Co-Investigator (7%, went to final interview with PI N. Lane and co-I A. Pomiankowski). Origins of Biology: How energy flow structures metabolism and heredity at the origin of life. Value: £2,965,963.43 (60 months) |
Start Year | 2018 |
Description | Mitochondrial Techniques Workshop 12-13 September 2017, UCL, London |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Two day, laboratory based workshop focused on techniques for mitochondrial research. I led the session on using UV/visible and infrared spectroscopy to gain qualitative, quantitative and structural information from the components of the mitochondrial respiratory chain It was held at University College London and was hosted by the UCL Consortium for Mitochondrial Research (CfMR) with support from The Physiological Society, the Biochemical Society and the British Pharmacological Society. |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.physoc.org/mitochondriaformandfunction/mitochondrial-techniques-workshop |
Description | Organisation of the 79th Harden Conference on 'Oxygen Evolution and Reduction - Common Principles' |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | This conference aimed at gathering the expertise of scientists working on photosystem II and cytochrome oxidases, two enzyme systems for which mechanistic and structural questions are common but which are rarely discussed comparatively. The format of the Harden meeting as a residential (comparable to a Gordon conference) fostered discussions and presentations of newly/unpublished ideas and data. The feedback received on the meeting from all the participants was extremely positive. |
Year(s) Of Engagement Activity | 2016 |
URL | https://www.biochemistry.org/Events/tabid/379/MeetingNo/79hdn/view/Conference/Default.aspx |
Description | Organisation of the 85th Harden Conference on 'Dynamic Membrane Complexes: Respiration and Transport' in Bonn, Germany |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | The programme of this residential conference was designed to bring leaders in the fields of molecular respiration together with scientists working at the forefront of membrane transport, membrane structural biology and lipid biochemistry to create a more complete understanding of respiration and transport and explore further the relationship between function and disease. The conference has received tremendous feedback and the organisation of a next edition is already well underway for 2021. |
Year(s) Of Engagement Activity | 2019 |
URL | https://biochemistry.org/events/85th-harden-conference-dynamic-membrane-complexes-respiration-and-tr... |
Description | Organisation of the Annual Meeting of the Bioenergetics group UK, Birkbeck, London |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | The 1-day Bioenergetics Christmas meeting was held at Birkbeck College on the 19th Dec 2017. It started with a keynote lecture by Prof Bill Rutherford FRS, from Imperial College, entitled 'Photosynthetic reaction centers: relating light, oxygen, survival and the energy limits' followed by 10 short talks from Post-docs and PhD students. Prof Rutherford gave a brilliant account of the state of the research in photosynthetic reaction centres, presenting some very exciting ideas and new perspectives to the field. He has certainly been very inspirational to the young researchers in the audience and has sparked some animated discussions among more senior scientists from which we all benefited over lunch. The presentations that followed from post-docs and PhD students were equally exciting and all were very thankful for the opportunity to present their work to an informed audience. The meeting was very well attended with people coming from across the country (and the world actually), the majority having last met a year or two ago at another edition of the Christmas meeting. I could hear people resurrecting plans of collaborations, other starting new ones (including myself) and there was a real sense of enthusiasm and optimism. It has been an excellent networking event for the UK bioenergetics community, with many very senior researchers present, discussing the meeting with junior colleagues. |
Year(s) Of Engagement Activity | 2017 |
Description | Poster presentation by 1st year Wellcome Trust PhD rotation student Gabriel Ing at the annual UK Bioenergetics group meeting - Queen Mary University of London, 16 December 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Gabriel presented his work in the form of a poster. This was his first participation in a scientific meeting and gave him exposure to the national bioenergetics community. |
Year(s) Of Engagement Activity | 2019 |
Description | Scientific presentation given by Dr Andrew Hartley at the Annual Meeting of the Bioenergetics group UK, Birkbeck, London |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Dr Andrew Hartley presented his latest results in a presentation entitled 'Cryo-EM studies of cytochrome c oxidase and respiratory supercomplexes from Saccharomyces cerevisiae'. |
Year(s) Of Engagement Activity | 2017 |
Description | Talk by Dr Andrew Hartley at the 85th Harden Conference in Bonn, Germany - 28 August 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Andrew presented his latest unpublished work on cryoEM of yeast respiratory supercomplexes. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.eventsforce.net/biochemsoc/frontend/reg/tAgendaWebsite.csp?pageID=26044&ef_sel_menu=343&... |
Description | Talk by Dr Andrew Hartley at the Annual Meeting of the Bioenergetics group UK, Cambridge - 14 December 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Dr Andrew Hartley presented our work to our UK scientific community on the determination of the structure of cytochrome c oxidase by cryoEM. People inquired in which journal they could find the details of our work which was very well received by the audience. |
Year(s) Of Engagement Activity | 2018 |
Description | TechMuses One-day visit from students from Gladesmore Community school to UCL |
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 | Every year, since 2018, I welcome to my lab at UCL twenty 14-15-year-old girls and their teachers from Gladesmore community school (http://www.gladesmore.com/), a less-privileged girl-only school in Haringey. I talk to them about my research and career path. The visits are in partnership with a charity called Techmuses that provide mentorship to school girls that are interested in STEM subjects. Each year the visit is a huge success and the school is immensely grateful for providing to their pupils such an open minding insight into STEM research. |
Year(s) Of Engagement Activity | 2018,2019,2020 |
Description | Technical workshop demonstrating the application of FTIR spectcroscopy to PhD students, postdocs and established scientists in the field of mitochondrial research |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | The course entitled 'Principles of Mitochondrial Biology, Metabolism and Bioenergetics in Health and Disease' was designed primarily for PhD students and post docs but also catered for more established academics seeking a deeper understanding of mitochondrial biology and techniques applicable to their research. In particular, the extent of the application of FTIR spectroscopy to biological studies is not well known so its dissemination to skilled scientists, at any stage of their career, has the potential to directly benefit their field of expertise. Advises were given to all participants on the applicability of the technology to their own research. |
Year(s) Of Engagement Activity | 2015 |
URL | http://mitochondria.cs.ucl.ac.uk/mip2015/ |