Automated high throughput high-resolution imaging
Lead Research Organisation:
King's College London
Department Name: Developmental Neurobiology
Abstract
Solving essential questions of biology requires the acquisition of large amount of data and excellent analytical approaches.
For research addressing biological problems using tissues and animals, the pace of progress is mostly hampered by the lack of technologies allowing to acquire and analyse large amount of images at high resolution in a short period of time.
Such technology has recently been built, in the form of a computer-controlled robotic device coupled to a confocal microscope. This high throughput equipment, called VAST, can automatically load, orient, image and redistribute hundreds of live embryos into multiwell plates. Imaging is done at subcellular resolution in record time, while keeping track of all the data to the redistributed animals for further studies. The computer not only acquire the data but also analyse them according to parameters defined by the specific research question investigated.
Such equipment is to yet available in the UK, except for Edinburgh. We therefore propose to acquire such equipment in London, for the benefit of a large set pf scientific programmes supported by the BBSRC. Moreover, we plan to open the equipment to a broader scientific community, in and around the capital (eg. Brighton, Cambridge, Bath, Bristol).
For research addressing biological problems using tissues and animals, the pace of progress is mostly hampered by the lack of technologies allowing to acquire and analyse large amount of images at high resolution in a short period of time.
Such technology has recently been built, in the form of a computer-controlled robotic device coupled to a confocal microscope. This high throughput equipment, called VAST, can automatically load, orient, image and redistribute hundreds of live embryos into multiwell plates. Imaging is done at subcellular resolution in record time, while keeping track of all the data to the redistributed animals for further studies. The computer not only acquire the data but also analyse them according to parameters defined by the specific research question investigated.
Such equipment is to yet available in the UK, except for Edinburgh. We therefore propose to acquire such equipment in London, for the benefit of a large set pf scientific programmes supported by the BBSRC. Moreover, we plan to open the equipment to a broader scientific community, in and around the capital (eg. Brighton, Cambridge, Bath, Bristol).
Technical Summary
Solving essential questions of biology requires the acquisition of large amount of data and excellent analytical approaches.
For research addressing biological problems using tissues (eg. organoids) and animals, the pace of progress is mostly hampered by the lack of technologies allowing to acquire and analyse large amount of images at high resolution in a short period of time.
Such technology has recently been built, in the form of a computer-controlled robotic device coupled to a confocal microscope. This equipment, called VAST (Vertebrate Automated Screening Technology), can automatically load, orient, image and redistribute hundreds of live embryos into multiwell plates. Imaging is done at subcellular resolution in record time, while keeping track of all the data to the redistributed animals for further studies. The computer not only acquire the data but also analyse them according to parameters defined by the specific research question investigated.
The system consists of the VAST BioImager Module, including a Large Particle Sampler and Dispenser Kit. The imaging system is based on a spinning disk confocal microscope. The attached computer workstation is controlling both VAST and confocal and is fully equipped with a tomography and data analysis software.
Such equipment is to yet available in the UK, except for Edinburgh. We therefore propose to acquire such equipment in London, for the benefit of a large set pf scientific programmes supported by the BBSRC (see Objectives). Moreover, we plan to open the equipment to a broader scientific community, in and around the capital (eg. Brighton, Cambridge, Bath, Bristol).
For research addressing biological problems using tissues (eg. organoids) and animals, the pace of progress is mostly hampered by the lack of technologies allowing to acquire and analyse large amount of images at high resolution in a short period of time.
Such technology has recently been built, in the form of a computer-controlled robotic device coupled to a confocal microscope. This equipment, called VAST (Vertebrate Automated Screening Technology), can automatically load, orient, image and redistribute hundreds of live embryos into multiwell plates. Imaging is done at subcellular resolution in record time, while keeping track of all the data to the redistributed animals for further studies. The computer not only acquire the data but also analyse them according to parameters defined by the specific research question investigated.
The system consists of the VAST BioImager Module, including a Large Particle Sampler and Dispenser Kit. The imaging system is based on a spinning disk confocal microscope. The attached computer workstation is controlling both VAST and confocal and is fully equipped with a tomography and data analysis software.
Such equipment is to yet available in the UK, except for Edinburgh. We therefore propose to acquire such equipment in London, for the benefit of a large set pf scientific programmes supported by the BBSRC (see Objectives). Moreover, we plan to open the equipment to a broader scientific community, in and around the capital (eg. Brighton, Cambridge, Bath, Bristol).
Publications
Nikolaou N
(2022)
Cytoplasmic pool of U1 spliceosome protein SNRNP70 shapes the axonal transcriptome and regulates motor connectivity.
in Current biology : CB
Taylor R
(2022)
Prematurely terminated intron-retaining mRNAs invade axons in SFPQ null-driven neurodegeneration and are a hallmark of ALS.
in Nature communications
Tuschl K
(2022)
Loss of slc39a14 causes simultaneous manganese hypersensitivity and deficiency in zebrafish.
in Disease models & mechanisms
Description | This sophisticated piece of equipment allowed 5 labs in London across three research institutions to screen for drugs affecting their biological process of interest. For at least two research programme the automated microscopy provided promising candidates that are explored further and will likely lead to publications in the next year. One main activity is aiming to find targets for a severe human disorder affecting individuals from birth, without any therapy to date (FOXG1 syndrome). |
Exploitation Route | The equipment will provide the means to identify drugs with strong potential for being clinical trial candidates. |
Sectors | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
Description | Drug discovery. But too early to give more details on which ones and how they will change human health. |
First Year Of Impact | 2023 |
Sector | Healthcare,Pharmaceuticals and Medical Biotechnology |
Impact Types | Societal |
Description | Using fish biodiversity to understand brain evolution |
Amount | £39,700 (GBP) |
Funding ID | BB/V018175/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2022 |
End | 10/2023 |
Title | Automated high resolution and high throughput screening platform |
Description | We installed and optimised a robot delivering single fish larvae to a confocal spinning disk which take confocal stacks of specific cell populations in the forebrain and quantify them automatically. The larvae are delivered back into their wells after imaging. This allow high speed high resolution imaging of larvae for drug or genetic screens. The equipment is made available for the whole of the zebrafish research community in London, involving KCL, UCL and the Francis Crick Institute. The equipment is used by scientists and clinicians. |
Type Of Material | Technology assay or reagent |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | We have just installed it. We predict this will allow many labs to screen for drugs modifying the pathology of many disease models and provide high-throughput results for drug and genetic screens needed to resolve complex pathways controlling normal developmental and physiological processes. |
Description | Collaboration with the MRC-funded Dementia Research Institute (DRI) |
Organisation | UK Dementia Research Institute |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | We provide the DRI with our expertise and understanding of the complex regulation of mRNAs in axons and dendrites of developing and degenerating neurons. Our previous findings on SFPQ has already been of great value for the field of ALS. Our continued interaction will allow us to share unpublished data bidirectionally and synergise in both basic and translational directions. |
Collaborator Contribution | The DRI is providing the interactions and exchanges of data that allows our research on local mRNA regulation and splicing factor functions in axons to develop more direct pre-clinical avenues. |
Impact | Just starting |
Start Year | 2022 |
Description | Cross London drug screening collaboration |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Sharing drug libraries and using same equipment to screen drugs for multiple biological processes and disorders |
Collaborator Contribution | Sharing drug libraries and using same equipment to screen drugs for multiple biological processes and disorders |
Impact | Outputs or outcome still to come |
Start Year | 2023 |
Description | Using fish biodiversity to understand brain evolution |
Organisation | Monash University |
Department | Australian Regenerative Medicine Institute (ARMI) |
Country | Australia |
Sector | Academic/University |
PI Contribution | We are providing our expertise in fish brain development and our unique skills and technology allowing cell transplantation in fish embryos. |
Collaborator Contribution | They are providing the shark species we need to do a comparative study of forebrain development. The sharks have a embryonic forebrain much more similar to mammals than the zebrafish and will contribute greatly in our understanding of early mechanisms not present in the zebrafish, providing the ease in accessing embryos and imaging them at the same time as developing similarly to mammalian early forebrain. |
Impact | Just starting |
Start Year | 2022 |
Description | Dev Neuro Academy |
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 | Organisation of a couple of weeks of interaction and research activities with school pupils under-represented at university level (schools having very few kids going to university). We make them familiar with university research and education and build their confidence in considering university education as attainable and interesting for them. |
Year(s) Of Engagement Activity | 2015,2016,2017,2018,2019,2022 |
URL | https://devneuro.org/cdn/public-engagement-dna.php |
Description | In2Science |
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 | Lab members involved in getting youth from disadvantaged background involved in STEM through activities and interactions across the academic year. |
Year(s) Of Engagement Activity | 2023 |
Description | Mini-conference with FOXG1 syndrome patients and family |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | A one day conference with scientific talks, presentations of communication alternatives and communication tools for patients, and discussion with patient families and therapists. The event was organised by CH in collaboration with FOXG1 Research foundation. |
Year(s) Of Engagement Activity | 2019 |