MICA: Multi-parametric and super-resolution imaging of amyloidogenic proteins
Lead Research Organisation:
University of Cambridge
Department Name: Chemical Engineering and Biotechnology
Abstract
Alzheimer's, like other neurodegenerative diseases, is caused by aberrant forms of proteins which tend to accumulate and aggregate into shapes, which are believed to be toxic to the brain cells of affected patients. The two proteins thought to cause Alzheimer's are called amyloid-beta and tau. The precise mechanisms by which these proteins aggregate into toxic forms are unknown, but there is accumulating evidence that the shape and size of forming aggregates is intricately linked to the onset and progression of disease. Yet there are no tools to study the growth of toxic aggregates in living cells, they are simply too small to be observed with traditional techniques. For the development of potential therapies against Alzheimer's, a microscopic understanding of the events leading to aggregation, and their consequence on affected cells, is crucial. Being able to observe protein aggregation in brain cells would permit us to relate the appearance of protein "clumps" with their toxic effect. Do affected cells malfunction? In what way? What aggregate species cause the cells to malfunction? Can we identify the toxic species leading cells to 'misbehave'? Can we inhibit the formation of "toxic shapes" in living cells through the addition of potential therapeutic agents? Can we stop the spreading of toxic species from cell-to-cell? Answers to these questions require radically new approaches to look into cells, at unprecedented resolution. In our group we have recently developed a new kind of microscope, a so called optical super-resolution microscope, that is so powerful that it is capable of visualising the shape of protein aggregates directly in cultured brain cells, which we use as model systems of disease. We were the first researchers to demonstrate that it is possible to obtain 'images' of toxic protein shapes in neurones, and here we propose to use this newly developed tool to shed new light on the mechanisms that lead to the onset and propagation of disease.
The aims of our proposed research project are: 1) to identify specific species of amyloid-beta and tau in neurones and other cells present in the brain and to relate the shape, and size of these species to the appearance of disease symptoms. 2) to study amyloid-beta and tau trafficking in and out of cells and to infer on the implications of this on the possible mechanisms of disease progression. 3) to see whether potential inhibitors of protein aggregation and propagation have an effect on what we observe within the cells we study. We will test several promising anti-aggregation anti-propagation compounds that our collaborators provide.
Through the development and application of advanced microscopic imaging techniques developed in our group we aim to gain insight into the molecular level processes that lie at the heart of Alzheimer's disease and other forms of dementia. Our techniques enable us to investigate the mechanisms that lead to the misfolding and spreading of proteins and their aggregation into toxic structures in live cell model systems at very high resolution, giving insight into the mechanisms of disease and its propagation. This understanding may help in the future search for potential therapeutic agents. The knowledge and tools generated here will provide a rational basis for the development of biomarkers/diagnostics that will enable physicians to: 1) detect the disease in its earliest stages when only biochemical changes are apparent; 2) identify the stage of the disease in order to tailor therapies for individual patients; and 3) monitor response to that treatment. Knowledge of these pathways will also provide targets for therapies to repair these pathways, thereby preventing or even reversing the disease.
The aims of our proposed research project are: 1) to identify specific species of amyloid-beta and tau in neurones and other cells present in the brain and to relate the shape, and size of these species to the appearance of disease symptoms. 2) to study amyloid-beta and tau trafficking in and out of cells and to infer on the implications of this on the possible mechanisms of disease progression. 3) to see whether potential inhibitors of protein aggregation and propagation have an effect on what we observe within the cells we study. We will test several promising anti-aggregation anti-propagation compounds that our collaborators provide.
Through the development and application of advanced microscopic imaging techniques developed in our group we aim to gain insight into the molecular level processes that lie at the heart of Alzheimer's disease and other forms of dementia. Our techniques enable us to investigate the mechanisms that lead to the misfolding and spreading of proteins and their aggregation into toxic structures in live cell model systems at very high resolution, giving insight into the mechanisms of disease and its propagation. This understanding may help in the future search for potential therapeutic agents. The knowledge and tools generated here will provide a rational basis for the development of biomarkers/diagnostics that will enable physicians to: 1) detect the disease in its earliest stages when only biochemical changes are apparent; 2) identify the stage of the disease in order to tailor therapies for individual patients; and 3) monitor response to that treatment. Knowledge of these pathways will also provide targets for therapies to repair these pathways, thereby preventing or even reversing the disease.
Technical Summary
Amyloid proteins such as Abeta and tau are known to misfold and, eventually, to aggregate into insoluble deposits.
Questions that remain unsolved include: What are the neurotoxic amyloid species? Can the misfolded state propagate from one cell to another and has this an impact on the neuropathology? Do extracellular chaperones impact on degradation or aggregation pathways of amyloid species? The applicant's group specialises in the development and application of advanced microscopy techniques for the functional study of protein self-assembly reactions in neurodegenerative disease. We will use these tools to address the following questions:
- Abeta and tau aggregates are likely to be composed of ensembles of oligomers with different sizes and conformations and potentially differing neurotoxicity. We will use novel fluorescence-based sensors to: a) characterise the biophysical properties of these ensembles in live cells with a spatial resolution on the molecular scale; and b) correlate their biophysical properties with effects on neuropathology.
- There is increasing evidence in the literature that intracellular Abeta plays an important role in disease. In addition, the propagation of tau pathology appears to be crucial in spreading the disease to non-affected brain areas. We aim to characterise the trafficking mechanisms responsible for amyloid proteins being taken up by cells and/or released in the extracellular space.
- We will screen for different inhibitors of Abeta or tau mediated neuropathology. Firstly, we will investigate different inhibitors of amyloid proteins propagation. Secondly, we will test the potential of extracellular chaperones to interfere with amyloid protein degradation or aggregation.
Questions that remain unsolved include: What are the neurotoxic amyloid species? Can the misfolded state propagate from one cell to another and has this an impact on the neuropathology? Do extracellular chaperones impact on degradation or aggregation pathways of amyloid species? The applicant's group specialises in the development and application of advanced microscopy techniques for the functional study of protein self-assembly reactions in neurodegenerative disease. We will use these tools to address the following questions:
- Abeta and tau aggregates are likely to be composed of ensembles of oligomers with different sizes and conformations and potentially differing neurotoxicity. We will use novel fluorescence-based sensors to: a) characterise the biophysical properties of these ensembles in live cells with a spatial resolution on the molecular scale; and b) correlate their biophysical properties with effects on neuropathology.
- There is increasing evidence in the literature that intracellular Abeta plays an important role in disease. In addition, the propagation of tau pathology appears to be crucial in spreading the disease to non-affected brain areas. We aim to characterise the trafficking mechanisms responsible for amyloid proteins being taken up by cells and/or released in the extracellular space.
- We will screen for different inhibitors of Abeta or tau mediated neuropathology. Firstly, we will investigate different inhibitors of amyloid proteins propagation. Secondly, we will test the potential of extracellular chaperones to interfere with amyloid protein degradation or aggregation.
Planned Impact
Over 820,000 people were affected by dementia in the UK in 2010, 24 million worldwide in 2005. This number is forecast to increase rapidly, making it one of the most pressing health issues in developed countries. The annual cost of dementia was over £23 billion in 2009. Our research is part of a global effort to assist the discovery of a cure for these devastating and costly diseases. Through the development and application of advanced microscopic imaging techniques developed in our group we aim to gain a mechanistic insight into the molecular level processes that lie at the heart of Alzheimer's disease and other forms of dementia. Our techniques enable us to investigate the mechanisms that lead to the misfolding of proteins and their aggregation into toxic structures in live cell model systems at molecular scale resolution, giving insight into the mechanisms of disease and its propagation. This understanding may help in the future search for potential therapeutic agents. The potential beneficiaries from this research are therefore:
- Neurobiologists studying neurodegenerative diseases (see previous section on academic beneficiaries)
- Pharmaceutical companies designing drugs will benefit from a better understanding of protein misfolding, aggregation, and dysfunction. They will also benefit from the technology we develop which could be optimised into methods for screening novel drugs and the investigation of their mode of action.
- Patients suffering from Alzheimer's disease and other forms of dementia, their carers and the community at large will benefit from a better understanding of the molecular and cellular events, which are involved in the onset and propagation of dementia. Drugs that may develop from such an understanding would greatly increase their quality and dignity of life as well as that of their relatives and carers.
- The project provides career opportunities for the named researchers through involvement and training in a cutting edge research environment on a topic of great socioeconomic importance. They will be trained in the development and application of state of the art molecular imaging methods, which finds use both in academic as well as in industrial research environments (e.g. in pharmaceutical companies).
- The National Physics laboratory will benefit through our collaboration in the development of optical super-resolution methods: the application of these techniques to address question of biomedical importance will provide incentives to further develop these methods (see letter of support). As the UK's national provider of measurement services, NPL will serve industry and academia on the whole with the provision of these technologies.
- The Neuroscience Consortium led by Prof. P. St. George-Hyslop, comprising research groups from across the UK and abroad will also benefit. Our technologies are critical to support the activities of these researchers, and our infrastructure and technical expertise will be made available to them free of charge.
- Neurobiologists studying neurodegenerative diseases (see previous section on academic beneficiaries)
- Pharmaceutical companies designing drugs will benefit from a better understanding of protein misfolding, aggregation, and dysfunction. They will also benefit from the technology we develop which could be optimised into methods for screening novel drugs and the investigation of their mode of action.
- Patients suffering from Alzheimer's disease and other forms of dementia, their carers and the community at large will benefit from a better understanding of the molecular and cellular events, which are involved in the onset and propagation of dementia. Drugs that may develop from such an understanding would greatly increase their quality and dignity of life as well as that of their relatives and carers.
- The project provides career opportunities for the named researchers through involvement and training in a cutting edge research environment on a topic of great socioeconomic importance. They will be trained in the development and application of state of the art molecular imaging methods, which finds use both in academic as well as in industrial research environments (e.g. in pharmaceutical companies).
- The National Physics laboratory will benefit through our collaboration in the development of optical super-resolution methods: the application of these techniques to address question of biomedical importance will provide incentives to further develop these methods (see letter of support). As the UK's national provider of measurement services, NPL will serve industry and academia on the whole with the provision of these technologies.
- The Neuroscience Consortium led by Prof. P. St. George-Hyslop, comprising research groups from across the UK and abroad will also benefit. Our technologies are critical to support the activities of these researchers, and our infrastructure and technical expertise will be made available to them free of charge.
Organisations
- University of Cambridge (Lead Research Organisation, Project Partner)
- Eberhard Karls University of Tübingen (Collaboration)
- University of Trieste (Collaboration)
- UiT The Arctic University of Norway (Collaboration)
- Zhejiang University (Collaboration)
- Utrecht University (Collaboration)
- University of Antwerp (Collaboration)
- Indian Institute of Technology Mandi (Collaboration)
- UNIVERSITY OF LEEDS (Collaboration)
- University of Bristol (Collaboration)
- National Institute of Health and Medical Research (INSERM) (Collaboration)
- Wellcome Trust (Collaboration)
- German Centre for Neurodegenerative Diseases (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- College of France (Collaboration)
- UNIVERSITY OF EXETER (Collaboration)
- Swiss Federal Institute of Technology in Lausanne (EPFL) (Collaboration)
- University of Vermont (Collaboration)
- Leibniz Association (Collaboration)
- Lund University (Collaboration)
- University of Würzburg (Collaboration)
- KING'S COLLEGE LONDON (Collaboration)
- Elan Pharmaceuticals (Project Partner)
- University of Würzburg (Project Partner)
- National Physical Laboratory (Project Partner)
- Max Planck Institutes (Project Partner)
Publications
![publication icon](/resources/img/placeholder-60x60.png)
Pang C
(2019)
On-Chip Super-Resolution Imaging with Fluorescent Polymer Films
in Advanced Functional Materials
![publication icon](/resources/img/placeholder-60x60.png)
Shigeoka T
(2019)
On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons.
in Cell reports
![publication icon](/resources/img/placeholder-60x60.png)
Arnon ZA
(2018)
Opal-like Multicolor Appearance of Self-Assembled Photonic Array.
in ACS applied materials & interfaces
![publication icon](/resources/img/placeholder-60x60.png)
Lamb JR
(2023)
Open-source software package for on-the-fly deskewing and live viewing of volumetric lightsheet microscopy data.
in Biomedical optics express
![publication icon](/resources/img/placeholder-60x60.png)
Pinotsi D
(2016)
Optical Super-Resolution Imaging of ß-Amyloid Aggregation In Vitro and In Vivo: Method and Techniques.
in Methods in molecular biology (Clifton, N.J.)
![publication icon](/resources/img/placeholder-60x60.png)
Vallejo Ramirez PP
(2019)
OptiJ: Open-source optical projection tomography of large organ samples.
in Scientific reports
![publication icon](/resources/img/placeholder-60x60.png)
Robbins M
(2021)
OptoGenie: an open-source device for the optogenetic stimulation of cells
in Journal of Open Hardware
![publication icon](/resources/img/placeholder-60x60.png)
Kaminski CF
(2016)
Probing amyloid protein aggregation with optical superresolution methods: from the test tube to models of disease.
in Neurophotonics
![publication icon](/resources/img/placeholder-60x60.png)
![publication icon](/resources/img/placeholder-60x60.png)
Van Tartwijk FW
(2022)
Protein Condensation, Cellular Organization, and Spatiotemporal Regulation of Cytoplasmic Properties.
in Advanced biology
![publication icon](/resources/img/placeholder-60x60.png)
Pinotsi D
(2016)
Proton Transfer and Structure-Specific Fluorescence in Hydrogen Bond-Rich Protein Structures.
in Journal of the American Chemical Society
![publication icon](/resources/img/placeholder-60x60.png)
Stephens AD
(2020)
Purification of Recombinant a-synuclein: A Comparison of Commonly Used Protocols.
in Biochemistry
![publication icon](/resources/img/placeholder-60x60.png)
Gielen F
(2017)
Quantitative Affinity Determination by Fluorescence Anisotropy Measurements of Individual Nanoliter Droplets.
in Analytical chemistry
![publication icon](/resources/img/placeholder-60x60.png)
Mela I
(2021)
Revealing Nanomechanical Domains and Their Transient Behavior in Mixed-Halide Perovskite Films
in Advanced Functional Materials
![publication icon](/resources/img/placeholder-60x60.png)
Wong HH
(2017)
RNA Docking and Local Translation Regulate Site-Specific Axon Remodeling In Vivo.
in Neuron
![publication icon](/resources/img/placeholder-60x60.png)
Scherer KM
(2022)
SARS-CoV-2 nucleocapsid protein adheres to replication organelles before viral assembly at the Golgi/ERGIC and lysosome-mediated egress.
in Science advances
![publication icon](/resources/img/placeholder-60x60.png)
Lu M
(2021)
Sea Cucumber-Derived Peptides Alleviate Oxidative Stress in Neuroblastoma Cells and Improve Survival in C. elegans Exposed to Neurotoxic Paraquat
in Oxidative Medicine and Cellular Longevity
![publication icon](/resources/img/placeholder-60x60.png)
Gaspar R
(2017)
Secondary nucleation of monomers on fibril surface dominates a-synuclein aggregation and provides autocatalytic amyloid amplification.
in Quarterly reviews of biophysics
![publication icon](/resources/img/placeholder-60x60.png)
Stephens AD
(2021)
Short hydrogen bonds enhance nonaromatic protein-related fluorescence.
in Proceedings of the National Academy of Sciences of the United States of America
![publication icon](/resources/img/placeholder-60x60.png)
Ströhl F
(2020)
Single Molecule Microscopy in Neurobiology
![publication icon](/resources/img/placeholder-60x60.png)
Ströhl F
(2017)
Single Molecule Translation Imaging Visualizes the Dynamics of Local ß-Actin Synthesis in Retinal Axons.
in Scientific reports
![publication icon](/resources/img/placeholder-60x60.png)
Zhong Wen
(2022)
Single multimode fiber for in vivo light-field encoded nano-imaging
![publication icon](/resources/img/placeholder-60x60.png)
Holcman D
(2018)
Single particle trajectories reveal active endoplasmic reticulum luminal flow.
in Nature cell biology
![publication icon](/resources/img/placeholder-60x60.png)
Charles N Christensen
(2022)
Spatio-temporal Vision Transformer for Super-resolution Microscopy
![publication icon](/resources/img/placeholder-60x60.png)
Ströhl F
(2017)
Speed limits of structured illumination microscopy.
in Optics letters
![publication icon](/resources/img/placeholder-60x60.png)
Laine RF
(2015)
Structural analysis of herpes simplex virus by optical super-resolution imaging.
in Nature communications
![publication icon](/resources/img/placeholder-60x60.png)
Fusco G
(2016)
Structural basis of synaptic vesicle assembly promoted by a-synuclein.
in Nature communications
![publication icon](/resources/img/placeholder-60x60.png)
Lu M
(2019)
Structural progression of amyloid-ß Arctic mutant aggregation in cells revealed by multiparametric imaging.
in The Journal of biological chemistry
![publication icon](/resources/img/placeholder-60x60.png)
Ströhl F
(2019)
Super-condenser enables labelfree nanoscopy.
in Optics express
![publication icon](/resources/img/placeholder-60x60.png)
Knight A
(2015)
Super-resolution fluorescent methods: where next for super-resolution?
in Methods and applications in fluorescence
![publication icon](/resources/img/placeholder-60x60.png)
Nugent E
(2017)
Super-resolution imaging of alpha-synuclein polymorphisms and their potential role in neurodegeneration.
in Integrative biology : quantitative biosciences from nano to macro
![publication icon](/resources/img/placeholder-60x60.png)
Poudel C
(2019)
Supercontinuum radiation in fluorescence microscopy and biomedical imaging applications
in Journal of the Optical Society of America B
![publication icon](/resources/img/placeholder-60x60.png)
Wunderlich LCS
(2021)
Superresolving the kidney-a practical comparison of fluorescence nanoscopy of the glomerular filtration barrier.
in Analytical and bioanalytical chemistry
![publication icon](/resources/img/placeholder-60x60.png)
Robbins M
(2021)
Synaptic tau: A pathological or physiological phenomenon?
in Acta neuropathologica communications
![publication icon](/resources/img/placeholder-60x60.png)
Teplensky MH
(2017)
Temperature Treatment of Highly Porous Zirconium-Containing Metal-Organic Frameworks Extends Drug Delivery Release.
in Journal of the American Chemical Society
![publication icon](/resources/img/placeholder-60x60.png)
Stephens AD
(2019)
The role of water in amyloid aggregation kinetics.
in Current opinion in structural biology
![publication icon](/resources/img/placeholder-60x60.png)
Stephens A
(2021)
The role of water mobility in protein misfolding
![publication icon](/resources/img/placeholder-60x60.png)
Lu M
(2020)
The structure and global distribution of the endoplasmic reticulum network are actively regulated by lysosomes.
in Science advances
![publication icon](/resources/img/placeholder-60x60.png)
Ströhl F
(2017)
Total internal reflection fluorescence anisotropy imaging microscopy: setup, calibration, and data processing for protein polymerization measurements in living cells.
in Methods and applications in fluorescence
![publication icon](/resources/img/placeholder-60x60.png)
Melo E
(2017)
TriPer, an optical probe tuned to the endoplasmic reticulum tracks changes in luminal H2O2
in BMC Biology
![publication icon](/resources/img/placeholder-60x60.png)
Crocker LB
(2022)
Tuning riboflavin derivatives for photodynamic inactivation of pathogens.
in Scientific reports
![publication icon](/resources/img/placeholder-60x60.png)
Hubin E
(2015)
Two distinct ß-sheet structures in Italian-mutant amyloid-beta fibrils: a potential link to different clinical phenotypes.
in Cellular and molecular life sciences : CMLS
![publication icon](/resources/img/placeholder-60x60.png)
Chambers JE
(2022)
Z-a1-antitrypsin polymers impose molecular filtration in the endoplasmic reticulum after undergoing phase transition to a solid state.
in Science advances
Description | We were able to obtain valuable original insight into the structure and state of neurotoxic protein aggregates involved in neurodegenerative diseases by developing and using super-resolution imaging methods to observe these proteins under physiological conditions and in-vivo (EP/H018301/1). In this research programme we have built on this work by studying the mechanism of growth and propagation of these species using super-resolution and fluorescence lifetime imaging techniques. At this stage we have published 4 papers demonstrating strong and original evidence for the potential prion-like toxicity and propagation of these toxic species. As well as providing fundamental understanding into the mechanism of neurodegenerative diseases, which we share with the research community through close collaboration with other groups in the Cambridge Neuroscience consortium, we actively participate in media outreach activities to widen public knowledge of ongoing progress in understanding the mechanism of Alzheimer's and Parkinson's disease. |
First Year Of Impact | 2014 |
Sector | Healthcare,Pharmaceuticals and Medical Biotechnology |
Impact Types | Policy & public services |
Description | "THE ROLE OF THE ALZHEIMER'S DISEASE RISK GENE PICALM IN BLOOD BRAIN BARRIER TRANSPORT, ALZHEIMER'S DISEASE AND AMYLOID ANGIOPATHY " |
Amount | £760,940 (GBP) |
Funding ID | MR/N012453/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2016 |
End | 05/2019 |
Description | (FUNCrystals) - Functional Organic Nanocrystals for Ultralong Phosphorescence Lifetime Bioimaging Applications |
Amount | € 224,934 (EUR) |
Funding ID | 101025385 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 07/2021 |
End | 06/2023 |
Description | 2019 exercise |
Amount | £400 (GBP) |
Organisation | European Biophysical Societies' Association |
Sector | Charity/Non Profit |
Country | Germany |
Start | 02/2018 |
End | 02/2018 |
Description | Alzheimer Research UK Cambridge Network travel grant |
Amount | £500 (GBP) |
Organisation | Alzheimer's Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2013 |
End | 10/2013 |
Description | British Biophysical Society Travel Grant |
Amount | £309 (GBP) |
Organisation | British Biophysical Society |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2018 |
End | 05/2018 |
Description | British Council Newton-Katip Celebi fund travel grant (Miranda Robbins) |
Amount | £200 (GBP) |
Organisation | British Council |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2016 |
End | 04/2017 |
Description | Cambridge ARUK Travel Grant |
Amount | £488 (GBP) |
Organisation | Alzheimer's Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2018 |
End | 05/2018 |
Description | Cambridge ARUK travel grant |
Amount | £300 (GBP) |
Organisation | Alzheimer's Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2019 |
End | 03/2019 |
Description | Cambridge ARUK travel grant (Miranda Robbins) |
Amount | £150 (GBP) |
Organisation | Alzheimer's Research UK |
Department | Alzheimers Research UK, Cambridge |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2017 |
End | 03/2017 |
Description | Cambridge Infinitus Research Centre |
Amount | £5,000,000 (GBP) |
Organisation | Infinitus |
Sector | Private |
Country | China |
Start | 09/2015 |
End | 08/2020 |
Description | EBSA bursary |
Amount | £330 (GBP) |
Organisation | European Biophysical Societies' Association |
Sector | Charity/Non Profit |
Country | Germany |
Start | 02/2018 |
End | 02/2018 |
Description | EMBO travel grant |
Amount | € 200 (EUR) |
Organisation | European Molecular Biology Organisation |
Sector | Charity/Non Profit |
Country | Germany |
Start | 10/2022 |
End | 10/2022 |
Description | Fellowship for the Winton-Berkeley Exchange program (Kavli Institute) |
Amount | £20,000 (GBP) |
Organisation | Kavli Energy NanoScience Institute |
Sector | Public |
Country | United States |
Start |
Description | IBIN Pump Prime Funding |
Amount | £11,000 (GBP) |
Organisation | United Kingdom Research and Innovation |
Department | Technology Touching Life |
Sector | Public |
Country | United Kingdom |
Start | 10/2020 |
End | 01/2021 |
Description | IBIN Pump-Prime Funding |
Amount | £10,717 (GBP) |
Organisation | United Kingdom Research and Innovation |
Department | Technology Touching Life |
Sector | Public |
Country | United Kingdom |
Start | 03/2021 |
End | 06/2021 |
Description | Liquid droplets and hydrogels in health and disease |
Amount | £400,000 (GBP) |
Funding ID | 203249/Z/16/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2017 |
End | 12/2021 |
Description | Liquid droplets and hydrogels:protein phasetransition in health and disease |
Amount | £3,111,483 (GBP) |
Funding ID | 203249/Z/16/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2017 |
End | 01/2021 |
Description | Marie Sklodowska-Curie Individual Fellowship |
Amount | € 225,000 (EUR) |
Funding ID | 101025385 |
Organisation | European Commission H2020 |
Sector | Public |
Country | Belgium |
Start | 09/2021 |
End | 08/2023 |
Description | Newnham College Travel Grant |
Amount | £731 (GBP) |
Organisation | University of Cambridge |
Department | Newnham College |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2018 |
End | 09/2018 |
Description | Newnham College Travel Grant |
Amount | £100 (GBP) |
Organisation | University of Cambridge |
Department | Newnham College |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2019 |
End | 06/2020 |
Description | Newnham College Travel Grant |
Amount | £600 (GBP) |
Organisation | University of Cambridge |
Department | Newnham College |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2019 |
End | 07/2020 |
Description | Oon Khye Beng Ch'Hia Tsio Studentships (Suil Collins) |
Amount | £1,500 (GBP) |
Organisation | University of Cambridge |
Department | Downing College, Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2017 |
Description | Pump Primimg Grant |
Amount | £3,100 (GBP) |
Organisation | Alzheimer's Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2021 |
End | 07/2022 |
Description | Research Fellowship Deutsche Forschungsgemeinschaft (DFG) |
Amount | € 140,400 (EUR) |
Funding ID | LA 3609/2-1 |
Organisation | German Research Foundation |
Sector | Charity/Non Profit |
Country | Germany |
Start | 04/2015 |
End | 03/2018 |
Description | Returning Carers Scheme |
Amount | £1,950 (GBP) |
Organisation | University of Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2019 |
End | 06/2019 |
Description | SUPUVIR Marie Curie Consortium |
Amount | € 4,017,699 (EUR) |
Funding ID | 722380 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 01/2017 |
End | 12/2021 |
Description | Shell Fund |
Amount | £500 (GBP) |
Organisation | University of Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2019 |
End | 04/2019 |
Description | Swiss National Science Foundation |
Amount | SFr. 72,000 (CHF) |
Organisation | Swiss National Science Foundation |
Sector | Public |
Country | Switzerland |
Start | 10/2014 |
End | 04/2016 |
Description | Travel Grant |
Amount | £462 (GBP) |
Organisation | University of Cambridge |
Department | Emmanuel College, Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 10/2022 |
End | 10/2022 |
Description | Travel Grant |
Amount | £600 (GBP) |
Organisation | Guarantors of Brain |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2021 |
End | 10/2021 |
Description | Travel Grant |
Amount | £300 (GBP) |
Organisation | Cambridge Philosophical Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2022 |
End | 10/2022 |
Description | Travel Grant |
Amount | £1,000 (GBP) |
Organisation | Alzheimer's Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2022 |
End | 02/2022 |
Description | Travel Grant |
Amount | £300 (GBP) |
Organisation | Cambridge Philosophical Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2021 |
End | 10/2021 |
Description | Travel Grant |
Amount | £243 (GBP) |
Organisation | University of Cambridge |
Department | Emmanuel College, Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 10/2021 |
End | 10/2021 |
Description | Travel Grant |
Amount | £970 (GBP) |
Organisation | Guarantors of Brain |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2021 |
End | 10/2022 |
Description | UK-KOREA COLLABORATION FOR NEURODEGENERATIVE DISEASE |
Amount | £9,490 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2016 |
End | 04/2017 |
Description | Building of a dSTORM set up with Prof Marcus Sauer |
Organisation | University of Wurzburg |
Country | Germany |
Sector | Academic/University |
PI Contribution | We contributed by building our own dSTORM set up and exchanging on the use of this technique for the study of neurodegenerative diseases |
Collaborator Contribution | Prof Marcus Sauer contributed by exchanging on his knowledge of the dSTORM technique and the photochemistry associated with it |
Impact | This collaboration resulted in our group having its own dSTORM set up Kaminski-Schierle GS, Sauer M, Kaminski CF, "Probing Amyloid Aggregation and Morphology In Situ by Multiparameter Imaging and Super-Resolution Fluorescence Microscopy," (2014) in Uversky VN, Lyubchenko YL, (eds) Bio-nanoimaging: Protein Misfolding & Aggregation, Academic Press, pp. 105-120 Kaminski Schierle GS, van de Linde S, Erdelyi M, Esbjörner EK, Klein T, Rees E, Bertoncini CW, Dobson CM, Sauer M, and Kaminski CF, "In Situ Measurements of the Formation and Morphology of Intracellular ß-Amyloid Fibrils by Super-Resolution Fluorescence Imaging", J. Am. Chem. Soc., 133 (33), pp 12902-12905, (2011). |
Start Year | 2008 |
Description | Cambridge Imperial Centre for Single Cell Analysis (T. Knowles, F. Hollfelder, J. Edel) |
Organisation | Imperial College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have written a joint grant proposal to set up a brain on chip platform. |
Collaborator Contribution | Joint grant proposal. |
Impact | Joint grant proposal written. |
Start Year | 2016 |
Description | Cambridge Imperial Centre for Single Cell Analysis (T. Knowles, F. Hollfelder, J. Edel) |
Organisation | University of Cambridge |
Department | MRC Cancer Unit |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have written a joint grant proposal to set up a brain on chip platform. |
Collaborator Contribution | Joint grant proposal. |
Impact | Joint grant proposal written. |
Start Year | 2016 |
Description | Computational study of the instrinsic fluorescence of amyloid fibrils with Ali Hassanali and Luca Grisanti |
Organisation | University of Trieste |
Country | Italy |
Sector | Academic/University |
PI Contribution | Experimental study of the fluorescence properties of amyloid and peptide fibrils |
Collaborator Contribution | Ab initio molecular dynamics simulations of the modeled peptide fibril systems (computational study) |
Impact | Paper accepted in JACS http://dx.doi.org/10.1021/jacs.5b11012 (multidisciplinary: spectroscopy, optical physics and theoretical chemistry) |
Start Year | 2013 |
Description | Correlative microscopy |
Organisation | Indian Institute of Technology Mandi |
Country | India |
Sector | Academic/University |
PI Contribution | Method development |
Collaborator Contribution | Method development |
Impact | Paper in preparation |
Start Year | 2022 |
Description | Electrophysiology with nanopipettes |
Organisation | College of France |
Country | France |
Sector | Academic/University |
PI Contribution | Building a microscope setup for combination with electrophysiology. |
Collaborator Contribution | Help with setting up electrophysiology measurements. |
Impact | Manuscript in preparation. |
Start Year | 2019 |
Description | Graphene microelectrode arrays for simultaneous electrical and fluorescence measurements on neurons with Antonio Lombardo and Andrea Ferrari |
Organisation | University of Cambridge |
Department | Cambridge Graphene Centre |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Growing and maintaining neuronal cell cultures, and imaging them on the graphene devices |
Collaborator Contribution | Fabricating the graphene microelectrode arrays, and making electrical measurements on them |
Impact | Multidisciplinary activity between biotechnology and electrical engineering |
Start Year | 2014 |
Description | Huntingtin propagation (Prof. G. Bates, Prof. H. Lashuel) |
Organisation | King's College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are sharing a PDRA who is funded by the CHDI foundation. We are collaborating on producing recombinant Huntingtin in order to determine the seeding capacity of the protein, which we will studied by TIRF microscopy. |
Collaborator Contribution | Gillian Bates was awarded the founding for the PDRA by the CHDI foundation. |
Impact | The collaboration is multi disciplinary, involving optical microscopy and biology. Prof. Hilal Lashuel from EPFL in Switzerland has joined this collaboration as he is an expert in the production of recombinant Huntingtin. |
Start Year | 2015 |
Description | Huntingtin propagation (Prof. G. Bates, Prof. H. Lashuel) |
Organisation | Swiss Federal Institute of Technology in Lausanne (EPFL) |
Country | Switzerland |
Sector | Public |
PI Contribution | We are sharing a PDRA who is funded by the CHDI foundation. We are collaborating on producing recombinant Huntingtin in order to determine the seeding capacity of the protein, which we will studied by TIRF microscopy. |
Collaborator Contribution | Gillian Bates was awarded the founding for the PDRA by the CHDI foundation. |
Impact | The collaboration is multi disciplinary, involving optical microscopy and biology. Prof. Hilal Lashuel from EPFL in Switzerland has joined this collaboration as he is an expert in the production of recombinant Huntingtin. |
Start Year | 2015 |
Description | Imaging of amyloid proteins present in cerebrospinal fluid with Prof Mathias Jucker |
Organisation | German Centre for Neurodegenerative Diseases |
Country | Germany |
Sector | Public |
PI Contribution | We contributed by imaging the samples provided by the collaborators on our dSTORM optical nanoscopy microscope. |
Collaborator Contribution | The group of Prof Mathias Jucker contributed samples of cerebrospinal fluid from mice and from humans |
Impact | An original paper has been published and further collaboration will take place. This is a collaboration between a lab which has access to rodent and human cerebrospinal fluid (our collaborators) and our lab which develops optical nanoscopy equipment. |
Start Year | 2013 |
Description | Integrated Microfluidic- Nanosensor System for Neuro- Functional Imaging and Neurotransmission Detection (Dr. E. Nugent) |
Organisation | University of Cambridge |
Department | Department of Physics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Jane is currently setting up a brain on chip platform to study amyloid propagation in live neurons. |
Collaborator Contribution | Dr. Eileen Nugent has been co-supervising Jane. |
Impact | Eileen Nugent, Clemens F. Kaminski and Gabriele S. Kaminski Schierle: Super-resolution imaging of alpha-synuclein polymorphisms and their potential role in neurodegeneration, Integr. Biol., 2017, Advance Article, doi:10.1039/C6IB00206D |
Start Year | 2016 |
Description | Interactions between aSynuclein and synaptic vesicles |
Organisation | Swiss Federal Institute of Technology in Lausanne (EPFL) |
Country | Switzerland |
Sector | Public |
PI Contribution | Prepared recombinant protein and purified synaptic vesicles for interaction studies |
Collaborator Contribution | Microfluidics-integrated nanophotonics-enhanced IR spectroscopy platform |
Impact | Paper in preparation. Molecular/structural biology and bionanophotonics |
Start Year | 2018 |
Description | Investigating the role of water in protein structure and aggregation |
Organisation | Swiss Federal Institute of Technology in Lausanne (EPFL) |
Country | Switzerland |
Sector | Public |
PI Contribution | Prepared recombinant protein alpha synuclein for aggregation studied in the presence of different salts. Morphology studies |
Collaborator Contribution | Used second harmonic scattering to determine mobility of water around fibrils |
Impact | Paper in preparation. Molecular/structural biology and physics/biophotonics |
Start Year | 2018 |
Description | Investigating the role of water in protein structure and aggregation |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Prepared recombinant protein alpha synuclein for aggregation studied in the presence of different salts. Morphology studies |
Collaborator Contribution | Runing and analysis of small angle neuron scattering data |
Impact | Paper in preparation, application for SANS beam time. Molecular biology and structural biology |
Start Year | 2018 |
Description | Investigating the role of water in protein structure and aggregation |
Organisation | University of Vermont |
Country | United States |
Sector | Academic/University |
PI Contribution | Prepared recombinant protein alpha synuclein for aggregation studied in the presence of different salts. Morphology studies |
Collaborator Contribution | Molecular dynamic simulations of peptide fragments in different salts |
Impact | Paper in preparation. Molecular/structural biology and physics/chemistry |
Start Year | 2018 |
Description | Mechanism of Interaction of Synaptic Vesicles Induced by a synuclein (Dr. DeSimone) |
Organisation | Imperial College London |
Department | Department of Life Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Our experiments, using super-resolution microscopy, revealed an inherent molecular mechanism enabling aS to promote the interaction between synaptic vesicles. |
Collaborator Contribution | They examined the validity of this mechanism by rationally designing and experimentally testing a variant of aS that was engineered to promote stronger interactions between vesicles. |
Impact | Fusco G, Pape T, Stephens AD, Mahou P, Costa A, Kaminski CF, Kaminski Schierle GS, Vendruscolo M, Veglia G, Dobson CM, De Simone A, "Structural basis of synaptic vesicle assembly promoted by a-synuclein", Nature Communications. (2016), 7: 12563. doi:10.1038/ncomms12563 There is currently a manuscript written up for a follow up project. |
Start Year | 2015 |
Description | Molecular chaperones as inhibitors of protein aggregation (Dr. Janine Kirstein, Berlin) |
Organisation | Leibniz Association |
Department | Leibniz-Institute for Molecular Pharmacology |
Country | Germany |
Sector | Academic/University |
PI Contribution | I have been invited to give a talk at the Leibniz-Institute for Molecular Pharmacology in Berlin |
Collaborator Contribution | A student from Dr. Kirstein's group will spend a Summer in my lab to test their chaperone related protein aggregation drugs |
Impact | not yet |
Start Year | 2016 |
Description | Optogentic control of ER morphology |
Organisation | Utrecht University |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | Sample preparation. Measuring ER dynamics with structured illumination microscopy. |
Collaborator Contribution | Hosting in the lab, provision of optogenetic tools, instruments and data analysis as well as help with experiments. |
Impact | Manuscript submitted. |
Start Year | 2018 |
Description | Photonic Chip Microscopy |
Organisation | Zhejiang University |
Country | China |
Sector | Academic/University |
PI Contribution | Support with AFM and fluorescence microscopy measurements. |
Collaborator Contribution | Fabrication of photonic chips. |
Impact | paper published: C Pang, et al., Advanced Functional Materials 29 (27), 1970188. |
Start Year | 2018 |
Description | SIM imaging of brain slices to investigate myelination with Robin Franklin |
Organisation | Wellcome Trust |
Department | Wellcome - MRC Cambridge Stem Cell Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Setting up the microscope, operation of the microscope, processing, reconstruction and analysis of the raw data, creation of a semi-automated image analysis protocol in Icy. |
Collaborator Contribution | Slicing of mouse brains, secondary anti-body staining, mounting of brain slices onto coverslip, statistical analysis of the data, biological interpretation. |
Impact | No publications yet, but promising results presented at various small talks - eg. in college, group meetings, to the IPES CDT |
Start Year | 2016 |
Description | Secondary nucleation of monomers on fibril surface dominates a-synuclein aggregation and provides autocatalytic amyloid amplification (Prof Emma Sparr/Prof Sara Linse) |
Organisation | Lund University |
Department | Department of Immunotechnology |
Country | Sweden |
Sector | Hospitals |
PI Contribution | Kinetic imaging of secondary nucleation reactions at the single molecule level with two colour direct stochastic Superresolution microscopy (dSTORM) |
Collaborator Contribution | Kinetic modelling of amyloid elongation reactions. Performed measurements in bulk samples. |
Impact | Paper in press at Quarterly Reviews of Biophysics Multidisciplinary: Chemistry, Physics |
Start Year | 2015 |
Description | Setting up a brain on chip platform for the study of prion like propagation in amyloid-related diseases (Prof. Knowles) |
Organisation | University of Cambridge |
Department | Department of Physics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Jane has been designing a new microfluidic based platform to sort and trap single neurons and to grow and differentiate them for live cell imaging. For this she has produced several PDMS devices, optimised flow conditions to guarantee fluidic isolation and is currently testing cell viability in these devices. She has further designed and implemented a device incubation chamber that can easily be adapted to fit on various microscope stages. |
Collaborator Contribution | Prof. Knowles PhD student Lianne Roode has been involved in this project and has helped with the design and evaluation of the original microfluidic design. |
Impact | We are currently writing up a manuscript on this. |
Start Year | 2016 |
Description | Single molecule translation imaging with Christine Holt and Bill Harris |
Organisation | University of Cambridge |
Department | Department of Physiology, Development and Neuroscience |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Carried out microscopy imaging and provided tools for data analysis. Continuous feedback for improvement of the imaging and preparation conditions. |
Collaborator Contribution | Prepared samples of Xenopus eyes for the study of the development of neural tract in the frog. Provided the biological question. |
Impact | None. Ongoing collaborations |
Start Year | 2014 |
Description | Structure of monomeric aSynuclein |
Organisation | University of Antwerp |
Country | Belgium |
Sector | Academic/University |
PI Contribution | Prepared recombinant protein alpha synuclein for aggregation studied in the presence of different salts. Morphology studies |
Collaborator Contribution | native mass spec and ion mobility mass spec |
Impact | Two papers in preparation. Molecular biology and structural biology |
Start Year | 2018 |
Description | Structure of monomeric aSynuclein |
Organisation | University of Exeter |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Prepared recombinant protein and purified synaptic vesicles for interaction studies |
Collaborator Contribution | Hydrogen-Deuterium Exchange Mass Spectroscopy |
Impact | Paper in preparation. Molecular biology and structural biology |
Start Year | 2016 |
Description | Structure of monomeric aSynuclein |
Organisation | University of Leeds |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Prepared recombinant protein alpha synuclein for aggregation studied in the presence of different salts. Morphology studies |
Collaborator Contribution | native mass spec and ion mobility mass spec |
Impact | Two papers in preparation. Molecular biology and structural biology |
Start Year | 2018 |
Description | Study of monomeric Tau propagation from cell to cell with Prof Eckard Mandelkow |
Organisation | German Centre for Neurodegenerative Diseases |
Country | Germany |
Sector | Public |
PI Contribution | We have applied multi parametric and super resolution imaging techniques to the study of Tau propagation from cell to cell |
Collaborator Contribution | Prof Eckard Mandelkow provided us with purified recombinant Tau protein, both unlabelled and fluorescently labelled. |
Impact | Michel CH, Kumar S, Pinotsi D, Tunnacliffe A, St George-Hyslop P, Mandelkow E, Mandelkow E-M, Kaminski CF, Kaminski Schierle GS, "Extracellular Monomeric Tau is Sufficient to Initiate the Spread of Tau Pathology", J. Biol. Chem. (2014), 289: 956-967. This collaboration is multi-disciplinary and involved biochemistry and physics |
Start Year | 2010 |
Description | Super-resolution imaging of macromolecules micelles assemblies with Ian Manners |
Organisation | University of Bristol |
Department | School of Chemistry |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Carried out super-resolution microscopy (dSTORM) imaging and feedbacks on how to prepare and design fluorescent probes for preparation of their micellar samples. |
Collaborator Contribution | Designed, prepared and synthetised the micellar structure used for the study of micelle elongation. |
Impact | None yet. But manuscript under preparation. |
Start Year | 2014 |
Description | Super-resolution imaging of nanotubes involved in the transfer of Tau from neuron to neuron (Luc Buee) |
Organisation | National Institute of Health and Medical Research (INSERM) |
Department | Lille (INSERM) |
Country | France |
Sector | Academic/University |
PI Contribution | We would carry out super-resolution imaging on samples |
Collaborator Contribution | Will provide cells, plasmids for expression of Tau and expertise in nanotubes |
Impact | Invited talk given by Dr Gabriele Kaminski Schierle in Lille for a seminar on New technologies and Neurosciences |
Start Year | 2015 |
Description | Synthetic 3D Neuronal Networks (Prof. Heutnik, Dr. Cesare) |
Organisation | Eberhard Karls University of Tübingen |
Department | Natural and Medical Sciences Institute |
Country | Germany |
Sector | Academic/University |
PI Contribution | We have written a proposal that we submitted to the VW Foundation. |
Collaborator Contribution | Joint proposal to VW Foundation. |
Impact | Joint proposal submitted |
Start Year | 2016 |
Description | Synthetic 3D Neuronal Networks (Prof. Heutnik, Dr. Cesare) |
Organisation | German Centre for Neurodegenerative Diseases |
Country | Germany |
Sector | Public |
PI Contribution | We have written a proposal that we submitted to the VW Foundation. |
Collaborator Contribution | Joint proposal to VW Foundation. |
Impact | Joint proposal submitted |
Start Year | 2016 |
Description | Synthetic 3D networks |
Organisation | German Centre for Neurodegenerative Diseases |
Department | Tübingen Research Campus |
Country | Germany |
Sector | Private |
PI Contribution | Written joint proposal to VW Foundation. |
Collaborator Contribution | Written joint proposal to VW Foundation. |
Impact | Written joint proposal to VW Foundation. |
Start Year | 2016 |
Description | Terrahertz spectroscopy of amyloid fibrils (Prof. Axel Zeitler) |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have formed L-Glu based nanostructures which display fluorescent properties. |
Collaborator Contribution | L-Glu based nanowires are currently investigated by THz spectroscopy in order to determine the origin of the fluorescence. |
Impact | First data sets are currently analysed. |
Start Year | 2017 |
Description | The Identification and development of small molecule inhibitors for the aggregation of amyloid beta - David Spring |
Organisation | University of Cambridge |
Department | Department of Chemistry |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The project was developed by a joint PhD researcher within the three groups. Project planning, microscopy and cell work are carried out in our group. |
Collaborator Contribution | - Project planning and the development of microfluidic techniques are carried out in the Hollfelder group. - The Spring group contributed small molecule compounds for screening. |
Impact | - Output: A joint PhD student who carries out the majority of the experimental work between the three laboratories. The project is multi-diciplinary. Microscopy and cell work are carried out in our group. Microfluidic assay development is being carried out in the the Hollfelder group. Organic synthesis of the small molecule screening libraries was carried out in the Spring group - Outcomes: None yet, but the research is still actively providing results which are expected to be submitted for publishing within the next few months. |
Start Year | 2014 |
Description | Translational cell biology of new microglial-related dementia genes (P. St. George Hyslop, O. Paulsen, G. Mallucci, D. Rubinsztein, D. Klenerman) |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have developed a microfluidic based neuronal platform in which we can amyloid protein propagation. We are currently setting up a new microfluidic device which will permit patch-clamp recordings to be taken of two individually (within the microfluidic device) connected neurons. This device will permit super-resolution recordings of propagating amyloid proteins to be imaged simultaneously with the electrophysiological recording. |
Collaborator Contribution | Patch clamp recordings will be undertaken by the collaborating partner. |
Impact | Written a joint grant application. |
Start Year | 2017 |
Description | Waveguide microscopy |
Organisation | UiT The Arctic University of Norway |
Country | Norway |
Sector | Academic/University |
PI Contribution | Building setup for imaging biological samples through waveguide microscopy. AFM measurements of waveguides. |
Collaborator Contribution | Fabrication of waveguides. |
Impact | paper published: Super-condenser enables labelfree nanoscopy: Florian Ströhl, Ida S Opstad, Jean-Claude Tinguely, Firehun T Dullo, Ioanna Mela, Johannes WM Osterrieth, Balpreet S Ahluwalia, Clemens F Kaminski, Optics express 27 (18), 25280-25292 |
Start Year | 2018 |
Description | Why do biological nanowires glow? (Dr. D. Credgington) |
Organisation | University of Cambridge |
Department | Department of Physiology, Development and Neuroscience |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We applied for a nanoCDT studentship. |
Collaborator Contribution | Application for nanoCDT studentship to study the intrinsic fluorescence related to amyloid proteins. |
Impact | Application for nanoCDT studentship. |
Start Year | 2017 |
Description | aSynuclein-lipid interaction |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Prepared recombinant alpha synuclein and brain extract lipid samples for aSyn/membrane interactions studies. Performed AFM analysis. |
Collaborator Contribution | Access to FastScan AFM in Pharmacology |
Impact | Paper in preparation. Molecular biology and structural biology |
Start Year | 2018 |
Description | dSTORM imaging of DNA origami with Ulrich Keuser |
Organisation | University of Cambridge |
Department | Cavendish Laboratory |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Carried out super-resolution microscopy imaging using DNA origami nano-structure. Carried out analysis and simulations based on observation proving the feasibility of the imaging. |
Collaborator Contribution | Designed, prepared and synthetised the DNA origami structure. |
Impact | None. Ongoing collaborations. Proof of principle of imaging of their DNA origami structures under our microscope. Foster further collaboration leading to offering student projects. |
Start Year | 2014 |
Description | super-resolution imaging of amyloid proteins with Prof Sara Linse |
Organisation | Lund University |
Country | Sweden |
Sector | Academic/University |
PI Contribution | The Laser Analytics Group is in the process of imaging amyloid protein fibril formation with super-resolution microscopy |
Collaborator Contribution | The group of Prof Sara Linse provided purified amyloid protein and gave a two-week tutorial to three members of the Laser Analytics group on purification of proteins |
Impact | This partnership is still young and we hope it will develop into publication on the amyloid fibril formation kinetics. This collaboration is multi-disciplinary, the Laser Analytics group being specialised in super-resolution imaging (physics, engineering) and the group or Prof Sara Linse in protein purification and biophysical characterisation of amyloid proteins |
Start Year | 2014 |
Description | super-resolution imaging of amyloid proteins with Prof Sara Linse |
Organisation | Lund University |
Country | Sweden |
Sector | Academic/University |
PI Contribution | The Laser Analytics Group is in the process of imaging amyloid protein fibril formation with super-resolution microscopy |
Collaborator Contribution | The group of Prof Sara Linse provided purified amyloid protein and gave a two-week tutorial to three members of the Laser Analytics group on purification of proteins |
Impact | This partnership is still young and we hope it will develop into publication on the amyloid fibril formation kinetics. This collaboration is multi-disciplinary, the Laser Analytics group being specialised in super-resolution imaging (physics, engineering) and the group or Prof Sara Linse in protein purification and biophysical characterisation of amyloid proteins |
Start Year | 2014 |
Description | ARUK Spring appeal |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | We participated in the preparation of an appeal letter and follow up letter to potential funders of ARUK regarding the use of emergency funding by ARUK. This was also followed by a blog post We expect some persons who received this appeal send fund to Alzheimer's Research UK for research on neurodegenerative diseases. |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.dementiablog.org/every-project-counts/ |
Description | Blog post on ARUK website on dSTORM (2014) |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Engage with patients, carers and families about research funded by ARUK Readers of the Alzheimer's Research UK might donate towards research. |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.dementiablog.org/10000-times-smaller-pinhead/ |
Description | CamBRAIN : Teaching children about neurons |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Teaching children about neurons |
Year(s) Of Engagement Activity | 2018 |
Description | Cambridge Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Engaging the public and children with demos related to microscopy and device development (for the study of diseases) |
Year(s) Of Engagement Activity | 2022,2023 |
Description | Episode of Elemental Ideas on Cambridge TV 25 Minute TV show about super-resolution microscopy |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Clemens Kaminski, Gabriele Kaminski Schierle, Colin Hockings, Florian Ströhl, Nathan Curry Episode of Elemental Ideas on Cambridge TV 25 Minute TV show about super-resolution microscopy 01/07/2016 Explaining research to the public through a video of our group's lab and research work, with interviews of the two group leaders and several postdoctoral research associates and PhD students. The videos can be accessed for free online. Elemental Ideas is Cambridge TV's science magazine programme. They've produced more than 50 programmes since August 2015, covering research topics including string theory, diabetes, exoplanets, vulcanology, epigenetics and the wildlife of New Zealand. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.cambridge-tv.co.uk/super-resolution-microscopy/ |
Description | Interview by ARUK at the Copenhagen AAIC conference |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | This activity resulted into engaging with readers of the Alzheimer's Research UK blog about research presented by Dr Claire Michel on a poster at the Alzheimer's Association International Conference 2014 With this interview funders of Alzheimer's Research UK received information regarding how their donations are used by researchers and what results researchers obtain. |
Year(s) Of Engagement Activity | 2014 |
Description | Interview on BBC Radio Cambridge 2014 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | This activity was a 3 minutes interview on super-resolution interview used in research on neurodegenerative diseases Engage with the wide public about advances in research on Alzheimer's disease |
Year(s) Of Engagement Activity | 2014 |
Description | Pint of Science Festival Cambridge |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Public lecture at Pint of Science Festival. |
Year(s) Of Engagement Activity | 2016 |
Description | PreLighter |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Writing highlight sections on interesting preprints for the PreLight website and twitter feed |
Year(s) Of Engagement Activity | 2018,2019 |
Description | Research Photography Exhibition |
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 | Finalist in STEM photography competition at Hughes Hall College, Cambridge |
Year(s) Of Engagement Activity | 2019 |
Description | Research exchange meeting with DAAD students |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | Organised a visit (lab tours and research lectures) for German Biophysics students funded under the "Studienstiftung" programme |
Year(s) Of Engagement Activity | 2016 |
Description | STEM in Song |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Encouraging school-aged girls to engage with the STEM subjects through music. Awards event with science demos, song launch at the LMB, music video at https://www.youtube.com/watch?v=7c4KMOWoZW4 . Reach: 15300 (according to Facebook insights) |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.youtube.com/watch?v=7c4KMOWoZW4 |
Description | Seminar on Science and Brewing |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Explaining science to the public |
Year(s) Of Engagement Activity | 2018 |
Description | Showcasing research to public in a hands on manner at the Cambridge Science Festival |
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 | Public/other audiences |
Results and Impact | Cambridge Science Festival Showcasing research to public in a hands on manner through various experiments organised in the dept of Chemistry including looking at neurons under a microscope. Explaining the group's research to the public Undertaken by several members of the group on a yearly basis since 2016 The Science Festival provides the public with opportunities to explore and discuss issues of scientific interest and concern and to raise aspirations by encouraging young people to consider a career in science, technology, engineering or mathematics. Each year, the Festival welcomes visitors to hundreds of events and receives extensive national and local media coverage. Over 170 event coordinators organise talks, interactive demonstrations, hands-on activities, film showings and debates with the assistance of around 1,000 staff and students from departments and organisations across the University and research institutions, charities and industry in the eastern region. In addition, over 150 people volunteer their time to act as stewards to ensure visitors have a safe and enjoyable Festival experience. |
Year(s) Of Engagement Activity | 2016,2017 |
URL | http://www.sciencefestival.cam.ac.uk/ |
Description | So you want to be a scientist?' experiment and speaking presentation |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Talking to school children about life as a scientist and GCSE options to take |
Year(s) Of Engagement Activity | 2018 |
Description | Superresolution public video |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Video interview and research video to explain superresolution microscopy in medical research to a lay audience. Currently >14000 views. |
Year(s) Of Engagement Activity | 2015 |
URL | https://www.youtube.com/watch?v=W-0GWbOFT3w |
Description | Talk and lab tour to funders of ARUK, Feb 2016 |
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 | Supporters |
Results and Impact | Engage with funders on the research carried out thanks to their donations |
Year(s) Of Engagement Activity | 2016 |
Description | Talk and lab tour to funders of ARUK, May 2015 |
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 | Supporters |
Results and Impact | Engage with funders on the research carried out thanks to their donations |
Year(s) Of Engagement Activity | 2015 |
Description | Talk on A short history of Microscopy, Cambridge |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Public lecture on A short history of Microscopy |
Year(s) Of Engagement Activity | 2017 |
Description | Talk, tour of the lab and Q&A for 15 employees of ARUK |
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 | Public/other audiences |
Results and Impact | This activity gave a clearer understanding to employees of ARUK and to readers of the ARUK blog of the work carried out by researchers studying dementia One employee of ARUK wrote a blog post on his visit, which increased the number of people reached through this activity. |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.dementiablog.org/tau-proteins/ |
Description | Tech Me Out team volunteer |
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 | Pint of Science Festival Cambridge |
Year(s) Of Engagement Activity | 2018 |