MultiUSer equipment for high-throughput, high-content analysis in Industrial and Cellular biotechnology (MUSIC)
Lead Research Organisation:
University of Manchester
Department Name: Chemistry
Abstract
Many of the projects in the Manchester Institute of Biotechnology involve a requirement for the sophisticated, detailed, and above all RAPID analysis of biological cell samples. An instrument called the Intellicyt iQue Screener PLUS permits this, and the aim of this proposal is to secure such an instrument for an extensive User Community in Manchester and elsewhere. The instrument is unique (multiple patents) and no such instrument is available within 200 miles of Manchester.
Technical Summary
Many of the projects in the Manchester Institute of Biotechnology involve a requirement for the sophisticated, detailed, and above all RAPID analysis of biological cell samples. The Intellicyt iQue Screener PLUS permits this, and the aim of this proposal is to secure such an instrument for an extensive User Community in Manchester and elsewhere. The instrument is unique (multiple patents) and no such instrument is available within 200 miles of Manchester.
Planned Impact
WHO WILL BENEFIT: Companies will benefit in a number of ways, by (i) gaining access to knowledge of methods used for the rapid analysis of cells using modern, high-throughput flow cytometry, and e.g. (ii) knowledge of how to improve tolerance to various compounds, whether they are substrates, intermediary metabolites, nutraceuticals, drugs, or bioactives in any kind of products. So far as industrial biotechnology more generally is concerned, companies will benefit from knowledge of a novel strategy for rapid cell analysis.
HOW WILL THEY BENEFIT: As is our practice, all pertinent data are made available via the Web, and OA publishing has long been our norm. We also hold frequent workshops in Manchester to assist dissemination of research results. We have pioneered in the Altmetrics field for digital dissemination - indeed a recent Nature article (Kwok R: Altmetrics make their mark. Nature 2013; 500:491-492) highlighted the fact that the PI's paper Hull D, Pettifer SR, Kell DB: Defrosting the digital library: bibliographic tools for the next generation web. PLoS Comput Biol 2008; 4:e1000204 was the most accessed in ANY PLoS journal, with over 53,000 accesses! (it is past 95,000 now) - the PI's paper Kell DB: Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genom 2009; 2:2 has over 85,000 accesses, increasing at ~50 per day).We shall work closely with University KT staff and industrial IP offices (UMIP in Manchester) to secure intellectual property rights for any useful inventions that we discover. Having secured IP, future development work can take place, and several routes to commercialisation can be explored. For example, all pharmaceutical companies have their own relevant groups, with whom we are in contact. Finally, having secured IP, we shall, of course, seek actively to communicate our scientific findings to the wider research community through scientific meetings, scholarly publications and press releases.
THE WIDER COMMUNITY: DBK is also a well known blogger and tweeter, and social media will provide a novel and useful means of disseminating our findings.
COMMUNICATIONS: We will communicate with relevant industrial partners both directly and via the meetings of relevant learned societies (we are members of several). In year three of the Project, we will organise a half-day meeting to explain our research to interested industrial scientists. However, we will also provide a video link to facilitate the participation of those who are unable to travel to Manchester.
HOW WILL THEY BENEFIT: As is our practice, all pertinent data are made available via the Web, and OA publishing has long been our norm. We also hold frequent workshops in Manchester to assist dissemination of research results. We have pioneered in the Altmetrics field for digital dissemination - indeed a recent Nature article (Kwok R: Altmetrics make their mark. Nature 2013; 500:491-492) highlighted the fact that the PI's paper Hull D, Pettifer SR, Kell DB: Defrosting the digital library: bibliographic tools for the next generation web. PLoS Comput Biol 2008; 4:e1000204 was the most accessed in ANY PLoS journal, with over 53,000 accesses! (it is past 95,000 now) - the PI's paper Kell DB: Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genom 2009; 2:2 has over 85,000 accesses, increasing at ~50 per day).We shall work closely with University KT staff and industrial IP offices (UMIP in Manchester) to secure intellectual property rights for any useful inventions that we discover. Having secured IP, future development work can take place, and several routes to commercialisation can be explored. For example, all pharmaceutical companies have their own relevant groups, with whom we are in contact. Finally, having secured IP, we shall, of course, seek actively to communicate our scientific findings to the wider research community through scientific meetings, scholarly publications and press releases.
THE WIDER COMMUNITY: DBK is also a well known blogger and tweeter, and social media will provide a novel and useful means of disseminating our findings.
COMMUNICATIONS: We will communicate with relevant industrial partners both directly and via the meetings of relevant learned societies (we are members of several). In year three of the Project, we will organise a half-day meeting to explain our research to interested industrial scientists. However, we will also provide a video link to facilitate the participation of those who are unable to travel to Manchester.
Publications
Borodina I
(2020)
The biology of ergothioneine, an antioxidant nutraceutical.
in Nutrition research reviews
Jindal S
(2019)
Involvement of multiple influx and efflux transporters in the accumulation of cationic fluorescent dyes by Escherichia coli.
in BMC microbiology
Jindal S
(2019)
Very rapid flow cytometric assessment of antimicrobial susceptibility during the apparent lag phase of microbial (re)growth.
in Microbiology (Reading, England)
Kell DB
(2021)
A protet-based, protonic charge transfer model of energy coupling in oxidative and photosynthetic phosphorylation.
in Advances in microbial physiology
Sadler JC
(2022)
SpeedyGenesXL: an Automated, High-Throughput Platform for the Preparation of Bespoke Ultralarge Variant Libraries for Directed Evolution.
in Methods in molecular biology (Clifton, N.J.)
Salcedo-Sora JE
(2021)
A palette of fluorophores that are differentially accumulated by wild-type and mutant strains of Escherichia coli: surrogate ligands for profiling bacterial membrane transporters.
in Microbiology (Reading, England)
Zhang S
(2019)
A brain-permeable inhibitor of the neurodegenerative disease target kynurenine 3-monooxygenase prevents accumulation of neurotoxic metabolites.
in Communications biology
Title | Ergothioneine: the new super antioxidant |
Description | Scientific animation |
Type Of Art | Film/Video/Animation |
Year Produced | 2020 |
Impact | Created to inform lay as well as professional audiences. |
URL | https://www.youtube.com/watch?v=SDiYMPpbUpk |
Title | How drugs and nutrients get into cells |
Description | Commissioned animation, 3.23 mins long. |
Type Of Art | Film/Video/Animation |
Year Produced | 2019 |
Impact | The animation was advertised throughout the University of Liverpool using internal communications. It has also been brought to the attention of collaborators across the world. Seeking to understand how drugs and nutrients get into living cells is not how a lot of textbooks portray it. |
URL | https://youtu.be/s23vNwLE-Jw |
Title | How drugs and nutrients get into cells |
Description | Scientific animation |
Type Of Art | Film/Video/Animation |
Year Produced | 2019 |
Impact | Freely available and created to reach and inform a wide audience. |
URL | https://www.youtube.com/watch?v=s23vNwLE-Jw |
Description | Novel high-throughput methods for flow cytometry. A novel method for rapid detection of antimicrobial resistance. |
Exploitation Route | Novel instrumentation. |
Sectors | Healthcare |
URL | https://umip.com/current-technologies/our-technologies/novel-method-for-rapid-antimicrobial-susceptibility-testing/ |
Title | Additional file 1: of Involvement of multiple influx and efflux transporters in the accumulation of cationic fluorescent dyes by Escherichia coli |
Description | Modal and mean uptake data for diS-C3(5) and Sybr green as described in the body of the paper. (XLSX 55 kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_1_of_Involvement_of_multiple_in... |
Title | Additional file 1: of Involvement of multiple influx and efflux transporters in the accumulation of cationic fluorescent dyes by Escherichia coli |
Description | Modal and mean uptake data for diS-C3(5) and Sybr green as described in the body of the paper. (XLSX 55 kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_1_of_Involvement_of_multiple_in... |
Description | Stellenbosch |
Organisation | University of Stellenbosch |
Country | South Africa |
Sector | Academic/University |
PI Contribution | Extraordinary (Honorary) Professor , Department of Physiological Science, Stellenbosch University Collaborative research in the areas of anti-microbial resistance, membrane transporters, dormant microbes as elements of supposedly non-communicable diseases, iron dysregulation, and enzyme improvement. |
Collaborator Contribution | Sharing of knowledge and analytical facilities at Stellenbosch, Manchester and Liverpool. |
Impact | Press release: Research opens door into new treatment options for chronic inflammatory diseases http://www.sun.ac.za/english/Lists/news/DispForm.aspx?ID=5104 Bezuidenhout J, Venter C, Roberts T, Tarr G, Kell D, Pretorius E (2020. Detection of citrullinated fibrin in plasma clots of RA patients and its relation to altered structural clot properties, disease-related inflammation and prothrombotic tendency. Front Immunol 11, 577523. DOI 10.3389/fimmu.2020.577523. bioRxiv link. DOI:10.1101/2020.05.28.121301. Venter C, Bezuidenhout JA, Laubscher GJ, Lourens PJ, Steenkamp J, Kell DB, Pretorius E (2020). Erythrocyte, platelet, serum ferritin and P-selectin pathophysiology implicated in severe hypercoagulation and vascular complications in COVID-19. Int J Mol Sci 21, 8234. DOI: 10.3390/ijms21218234 Pretorius E, Venter C, Laubscher GJ, Lourens PJ, Steenkamp J, Kell DB (2020) Prevalence of readily detected amyloid blood clots in 'unclotted' Type 2 Diabetes Mellitus and COVID-19 plasma: A preliminary report. Cardiovasc Diabetol 19, 193. DOI 10.1186/s12933-020-01165-7. Prevalence of amyloid blood clots in COVID-19 plasma. medRxiv 2020.2007.2028.20163543v20163541. DOI 10.1101/2020.07.28.20163543. Grobler C, Maphumulo SC, Grobbelaar LM, Bredenkamp J, Laubscher J, Lourens PJ, Steenkamp J, Kell DB, Pretorius E. (2020). COVID-19: The Rollercoaster of Fibrin(ogen), D-dimer, von Willebrand Factor, P-selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes. Int J Mol Sci 21:5168. DOI: 10.3390/ijms21145168. Preprint at Grobler C, Bredenkamp J, Grobbelaar M, Maphumulo S, Laubscher J, Steenkamp J, Kell DB, Pretorius E (2020): COVID-19: The Rollercoaster of Fibrin(ogen), D-dimer, von Willebrand Factor, P-selectin and their interactions with endothelial cells, platelets and erythrocytes. Preprints.org 2020:202007.200142/v202001. Nunes JM, Fillis T, Page MJ, Venter C, Lancry O, Kell DB, Windberger U, Pretorius E (2020) Gingipain R1 and lipopolysaccharide from Porphyromonas gingivalis have major effects on blood clot morphology and mechanics. Front Immunol. 11, 1551. DOI: 10.3389/fimmu.2020.01551 Olsen I, Kell DB, Pretorius E (2020). Is Porphyromonas gingivalis involved in Parkinson's disease? Eur J Clin Microbiol Infect Dis, https://doi.org/10.1007/s10096-020-03944-2. DOI: 10.1007/s10096-020-03944-2. Kell DB, Heyden EL Pretorius, E. (2020) The biology of lactoferrin, an iron-binding protein that can help defend against viruses and bacteria. FrontiersIn Immunol 11, 1221. DOI: 10.3389/fimmu.2020.01221. Borodina I, Kenny LC, McCarthy CM, Paramasivan K, Pretorius R, Roberts TJ, van der Hoek SA, Kell DB (2020). The biology of ergothioneine, an antioxidant nutraceutical. Nutr Res Rev. 33, 190-217. Pubmed 32051057. DOI: 10.1017/S0954422419000301 de Villiers S, Bester J, Kell DB, Pretorius E (2019) Erythrocyte health and the possible role of amyloidogenic blood clotting in the evolving haemodynamics of female migraine-with-aura pathophysiology: Results from a pilot study. Frontiers Neurol 10, 1262. de Villiers S, Bester J, Kell DB, Pretorius E: Erythrocyte health and the possible role of amyloidogenic blood clotting in the evolving haemodynamics of female migraine-with-aura pathophysiology: Results from a pilot study. Cephalalgia 2019; 39:150-151 Adams B, Nunes JM, Page MJ, Roberts T, Carr J, Nell TA, Kell DB, Pretorius E (2019) Parkinson's disease: a systemic inflammatory disease accompanied by bacterial inflammagens. Front Aging Neurosci 11, 210. Preprint: bioRxiv 2019:646307v646301. DOI: 10.3389/fnagi.2019.00210 Visser MJE, Kell DB, Pretorius E (2019): Bacterial dysbiosis and translocation in psoriasis vulgaris. Front Cell Infect Microbiol 7, 9. DOI: doi: 10.3389/fcimb.2019.00007 Pretorius L, Kell DB, Pretorius E. (2018). Iron dysregulation and dormant microbes as causative agents for impaired blood rheology and pathological clotting in Alzheimer's type dementia. Frontiers in Neurosci 12, 851. DOI: 10.3389/fnins.2018.00851 de Waal GM, Engelbrecht L, Davis T, de Villiers WJS, Kell DB, Pretorius E (2018) Correlative Light-Electron Microscopy detects lipopolysaccharide and its association with fibrin fibres in Parkinson's Disease, Alzheimer's Disease and Type 2 Diabetes Mellitus. Sci. Rep. 8, 16798. DOI: 10.1038/s41598-018-35009-y. Pretorius E, Bester J, Page MJ, Kell DB (2018): The potential of LPS-binding protein to reverse amyloid formation in plasma fibrin of individuals with Alzheimer-type dementia. Frontiers Aging Neurosci 10, 257. DOI: 10.3389/fnagi.2018.00257 Kell DB, Pretorius E (2018) To what extent are the terminal stages of sepsis, septic shock, SIRS, and multiple organ dysfunction syndrome actually driven by a toxic prion/amyloid form of fibrin? Semin Thromb Hemost 44, 224-238. PMID 28778104. DOI: 10.1055/s-0037-1604108. PRIZE for MOST VIEWED Open Access paper in the journal that year Kell DB, Pretorius E (2018) No effects without causes. The Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases: evidence and consequences. Biol Rev 93, 1518-1557. PMID 29575574. doi: 10.1111/brv.12407 Pretorius E, Page MJ, Mbotwe S, Kell DB (2018) Lipopolysaccharide-binding protein (LBP) can reverse the amyloid state of fibrin seen or induced in Parkinson's disease. PlosOne 13, e0192121. DOI: 10.1371/journal.pone.0192121 Pretorius E, Page MJ, Hendricks L, Nkosi NB, Benson SR, Kell DB (2018) Both lipopolysaccharide and lipoteichoic acids potently induce anomalous fibrin amyloid formation: assessment with novel Amytrackerâ„¢ stains. J R Soc Interface 20170941. Pubmed. DOI: 10.1098/rsif.2017.0941 Pretorius, E., Page, M.J., Engelbrecht, L., Ellis, G.C., and Kell, D.B. (2017). Substantial fibrin amyloidogenesis in type 2 diabetes assessed using amyloid-selective fluorescent stains. Cardiovasc Diabetol 16, 141. PMID 29096623. doi: https://doi.org/10.1186/s12933-017-0624-5. Pretorius E, Mbotwe S, Kell DB (2017) Lipopolysaccharide-binding protein (LBP) reverses the amyloid state of fibrin seen in plasma of type 2 diabetics with cardiovascular comorbidities. Sci Rep 7, 9680 doi:10.1038/s41598-017-09860-4 Pretorius E, Page MJ, Henricks L, Nkosi NB, Benson SR & Kell DB (2017) Both lipopolysaccharide and lipoteichoic acids potently induce anomalous fibrin amyloid formation: assessment with novel Amytrackerâ„¢ stains. BioRxiv 143867. DOI: https://doi.org/10.1101/143867 Kell, D. B. & Pretorius, E. (2017). Proteins behaving badly. Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting. Progr Biophys Mol Biol 123, 16-41. PMID 27554450. DOI: 10.1016/j.pbiomolbio.2016.08.006. Pretorius, E., Akeredolu, O.-O., Soma, P. & Kell, D.B. (2017). Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability. Exp Biol Med. 242, 355-373. PMID 27889698. DOI: 10.1177/1535370216681549 |
Start Year | 2017 |