Microbioleg A Biodechnoleg

Harneisio Ac Ymdrin Â Microbioleg

Nod is-thema microbioleg a biodechnoleg yw ceisio deall y prosesau sydd wrth wraidd twf microbau a manteisio arnynt, yn ogystal â'u rhyngweithiadau â'u lletywr a'u hamgylchedd.

Fel cartref y ganolfan ymchwil BEACON ryngddisgyblaethol gwerth miliynau o bunnau, rydym yn harneisio dealltwriaeth ffwngaidd a bacterol. Mae hyn yn caniatáu i ni ymladd gwrthiant gwrthffyngol, a dod o hyd i ddefnydd newydd o facteria er mwyn mynd i'r afael ag amrywiaeth o heriau iechyd. Rydym yn ceisio nodi marcwyr newydd a fydd yn ein helpu i ragweld ffactorau risg mewn perthynas â datblygu heintiau difrifol ymhlith pobl ac anifeiliaid.

Meysydd Ffocws Ymchwil Microbioleg A Biodechnoleg

Rydym yn parhau i ymchwilio i lwybrau ymchwil i'r ffordd y gellir defnyddio bacteria ac ensymau CYPs gwahanol mewn meddygaeth a biodechnoleg. Rydym yn gweithio gyda chlinigwyr, peirianwyr a diwydiant i optimeiddio a dod o hyd i ddulliau newydd o ddefnyddio bacteria mewn amrywiaeth o gyd-destunau. Rydym yn cydweithio â grwpiau ymchwil byd-eang a phartneriaid diwydiannol i ddeall prosesau microbiolegol amrywiol i ddatblygu biodechnoleg newydd

Gwrthiant Gwrthffyngol

Mae mwy na 190 o rywogaethau yn perthyn i'r genus Mycobacterium. Ymhlith y rhain, mae llawer yn bathogenig i bobl ac anifeiliaid. Yn fyd-eang, mae clefydau ffwngaidd yn arwain at fwy o farwolaethau blynyddol na malaria neu TB. Mae ein prif ffocws mewn perthynas â gwrthiant gwrthffyngol mewn pathogenau clinigol ac amaethyddol megis rhywogaeth Candida, rhywogaeth Aspergilws, rhywogaeth Cryptococcus a Mycosphaerella graminicola.

Yn yr is-thema mae gennym ffocws penodol ar deulu protein CYP, y profwyd ei fod yn gysylltiedig â rhwystro sawl rhywogaeth o Mycobacterium. Mae CYPs (yn enwedig CYP51) ac ensymau eraill yn ymwneud â chyfosod sterolau, fel targedau therapïau gwrthffyngol.

Harneisio Bacteria

Gan ddechrau ar fan dechrau symbiosis lletya bacteria, ar y dechrau, roedd y llinyn penodol hwn o ymchwil yn caniatáu i ni dorri tir newydd o fewn rheoli fectorau pryfed clefyd gan dalu sylw penodol i'r rhai o bwysigrwydd meddygol neu amaethyddol. Gan ddefnyddio proses a elwir yn ymyrraeth RNA; gallwn ddefnyddio dwy haen o benodolrwydd o ran targedu fector pryfed clefyd yn unig, heb achosi fawr ddim difrod cyfochrog.

Gwnaeth yr ymchwil a'r wybodaeth sylfaenol yma olygu y gellid cymryd naid o facteria, sy'n bresennol mewn pryfed, i rywogaethau bacteria sy'n cytrefu tiwmorau. Mae'r bacteria hyn yn ffynnu yn y tiwmorau hyn oherwydd y maetholion penodol a ddarperir gan yr amgylchedd hwn ac anallu'r system imiwnedd i adnabod eu presenoldeb yn y tiwmor. Mae'r ddealltwriaeth wyddonol sylfaenol hon yn ein galluogi i optimeiddio'r bacteria hyn i ffynnu yn yr amgylchedd hwn a darparu llwythau talu therapiwtig ar yr un pryd a fydd yn atal y tiwmor rhag tyfu a lledaenu.

Streptomyces: Bacteria Pridd Cyfeillgar

Bacteria pridd yw streptomyces sy'n cynhyrchu 70% o'r gwrthfiotigau a ddefnyddir mewn meddygaeth. Oherwydd lledaeniad y gwrthiant i lawer o wrthfiotigau rheng flaen, mae angen i ni ddod o hyd i rai newydd ar fyrder. Rydym yn cydweithio â gwyddonwyr rhyngwladol i ddarganfod rhywogaethau newydd sydd o bosibl yn cynhyrchu gwrthfiotigau newydd a deall cynhyrchiant naturiol gwrthfiotigau (gwrthfiosis) yn yr amgylchedd.

Rydym hefyd yn ceisio nodi potensial Streptomyces fel deunyddiau byw a pheiriannydd pridd. Rydym yn ymchwilio i'r ffordd o fanteisio ar gynhyrchion eraill megis proteinau hydroffobig a ‘nanogelloedd’ protein. Rydym hefyd yn astudio addasiad microbau a biobeirianneg atgasedd dŵr ac adlyniad/agregu deunyddiau naturiol ac wedi'u gweithgynhyrchu a gwrthiant i wrthfiotigau a metelau yn enwedig mewn pridd sydd wedi'i lygru â metel.

Canlyniadau Ymchwil

Rydym yn datblygu'r defnydd o facteria i reoli poblogaethau pryfed, gan nodi biofarcwyr er mwyn helpu i ragweld heintiau ymledol ymhlith pobl ac anifeiliaid. Nod ein hymchwil benodol i CYPs yw deall swyddogaeth eu proteinau. Ein nod yw harneisio bacteria, swyddogaethau CYP a'u llofnodion biolegol i drin clefyd a rheoli heriau yn llwyddiannus mewn amaethyddiaeth, i gyd gyda'r nod uniongyrchol o wella iechyd a llesiant. Mae ein gwaith yn datblygu moleciwlau ac ymchwil gweithredol newydd gan alluogi therapïau newydd a dealltwriaeth well o wrthiant cyffuriau, gan deilwra ymatebion unigol i therapi a chymwysiadau bio-dechnegol.

Colonies of Streptomyces producing a blue antibiotic

Tawelu Genynnau Mewn Pryfed Di-Fodel

Mae'r dechnoleg rydym wedi'i datblygu yn cynnig mesur rheoli poblogaeth wedi'i dargedu ar gyfer pryfed plâu. Mae'r animeiddiad hwn yn esbonio sut y gellir defnyddio symbiontiaid bacterol i gyflawni ymyrraeth RNA parhaus yn y grŵp mwyaf amrywiol o anifeiliaid, sef y pryfed.

Bacteria Sy'n Targedu Tiwmorau

Light producing tumour targetting bacteria

Bacteria Sy'n Targedu Tiwmorau

Rydym yn defnyddio bacteria i oleuo tiwmorau a darparu gwybodaeth er mwyn atal celloedd tiwmorau rhag tyfu. Nid oes gan y llwythau talu therapiwtig a ddarperir gan y bacteria y sgil effeithiau.

Ewch i Bodlediad 'Exploring Global Problems' i wrando ar gyfweliad yr Athro Dyson am y maes ymchwil hwn.

Rheoli Heintiau Ffwngaidd

Rheoli Heintiau Ffwngaidd

Mae heintiau ffwngaidd yn costio miliynau i'r diwydiant amaethyddol bob blwyddyn, o ganlyniad i gnydau wedi'u difrodi ac wedi'u dinistrio. Daw ffwngleiddiaid yn llai effeithiol wrth i ffyngau targed ddatblygu ymwrthedd iddynt. Ond mae'r angen i ddefnyddio mwy o ffwngleiddiaid o hyd yn arwain at niwed ecolegol hefyd.

Roedd yn bwysig datblygu ffwngleiddiad a fyddai'n llwyddo i ddinistrio'r ffwng targed heb amharu ar brosesau y tu mewn i'r lletywr, boed hynny'n blanhigyn neu'n anifail. Drwy gymryd y cam hwn, byddai ffwngleiddiaid yn fwy effeithiol, a byddai llai o niwed ecolegol

Nodi Biofarcwyr I Ragweld Heintiau Ymledol Ymhlith Pobl Ac Anifeiliaid

Mae micro-organebau sy'n achosi heintiau ymledol difrifol (e.e. sepsis) ac sy'n gysylltiedig â lefelau uchel o afiachusrwydd a marwolaeth, yn gyfrifol am ran helaeth o lwyth clefydau ledled y byd. Mae fy ngrŵp yn canolbwyntio ar asesu ymateb celloedd lletyol a chelloedd microbau er mwyn nodi patrymau mewn heintiau lleol (croen, ysgyfaint neu goludd) sy'n rhagweld pa mor debygol ydyw y bydd yr haint yn troi'n ddifrifol (gwaed). Mae ein hymchwil yn nodi biofarcwyr a fydd yn helpu'r GIG i ragweld y bobl hynny sy'n wynebu risg o ddatblygu haint difrifol ac yn helpu i achub bywydau.

Researchers looking at microscope image on digital screen

Biofarcwyr Lletyol A Bacterol I Ragweld Sepsis

Mae amcangyfrifon cyfredol yn awgrymu bod sepsis yn cyfrif am tua 20% o'r holl farwolaethau byd-eang - 11 miliwn o bobl y flwyddyn, sy'n syfrdanol. Mae angen rhagfynegyddion cynnar syml o syndrom sepsis i nodi cleifion sydd mewn perygl. Mewn cydweithrediad â chydweithwyr ym Mwrdd Iechyd Prifysgol Hywel Dda, ymchwilir i gasgliadau wedi'u harchifo o Escherichia coli prawf gwaed positif ar gyfer cynnwys eu genynnau a'u gallu i gynhyrchu ymatebion imiwn ynghyd â chofnodion meddygol y cleifion. Bydd y data sy'n deillio o hynny o'r lletywr a'r pathogen yn darparu ffactorau risg newydd pwysig er mwyn rhagweld sepsis.

Mae Rhyngweithiadau Rhwng Organeb Letyol A Phathogen Yn Bwysig I Symudiad Campylobacter Jejuni Fro

Mae'r DU yn hunangynhaliol mewn cig ieir, sy'n ffynhonnell protein fforddiadwy. Mae Campylobacter yn organeb bwysig sy'n gyfrifol am wenwyn bwyd mewn pobl oherwydd ei gallu i ymledu o berfeddion yr iâr i gyhyrau a'r afu. Mewn cydweithrediad â chydweithwyr yng Ngholeg Gwledig yr Alban, yn Newcastle, Caerlŷr ac â rhanddeiliaid diwydiannol, mae ein gwaith yn y prosiect hwn yn archwilio genynnau pwysig mewn Campylobacter, ac arwyddion imiwnedd pwysig yn yr iâr sy'n ffafrio ymatebion ymledol a all leihau bioddiogelwch bwyd. Bydd y data canlyniadol yn llywio mesurau bioddiogelwch newydd ar gyfer y diwydiant ieir.

Partneriaid Cydweithredol a Diwydiant

BASF
Defence Science and Technology Laboratory
Tata Steel
Nippon Sheet Glass group
Total Water Products
Hot Tubs UK/Eco3Spa
Engineered Biodesign Ltd
Demuris
Biotage
Quizslides
British Geological Survey
Rothamsted Research
Rothamsted Research
National Institute for Agricultural Botany
St Jude’s Research Hospital for Children Memphis (USA)
Woods Hole Oceanographic Institute (USA)
Aberystwyth University
Bangor University
Cardiff University
University of South Wales
Manchester University
Lausanne University (Switzerland)
Trinity College Dublin (Ireland)
University of Tennessee Health Science Centre, Memphis (USA).
University of Illinois at Urbana-Champaign (USA)
University of Florida (USA)
Vanderbilt University, Nashville (USA)

Prosiectau Ymchwil Cysylltiedig

ERDF/ Welsh Government BEACON Centre of Excellence in Biorefinery (2010-22)
National Institutes of Health (USA) Novel mechanisms of azole resistance in Candida albicans (2012-17;2017-22).
BBSRC. Two response mode grants currently.
EPSRC
European Commission - Horizon 2020, Marie Sklowdowska Curie Individual Fellowship support for DR Remi Zallot
Optimising symbiont-mediated RNA interference as a control measure for Western Flower Thrips and Tomato Spotted Wilt Virus
Symbiont-Mediated RNAi in Aedes aegypti
Use of RNAi to enhance effectivity of methods of Colorado Potato Beetle control
EXPLOITING ONCOTROPIC BACTERIA FOR EARLY DETECTION OF COLORECTAL CANCER
A NOVEL RNAI THERAPY FOR SOLID TUMOURS
Development of advanced corrosion-resistant coatings with synthetic biology-inspired protein technologies
Phase I and Phase II Development of a synbio-inspired composite adhesive for transparent defense materials
Developing a novel protein-based coating technology for anti-corrosion of magnesium light alloy materials
Sanitising efficacy of a new Hot Tub Water enzyme water treatment product
Determining the efficacy of products for bacterial biofilm prevention and removal for the wet leisure industry
Incorporation of microbial organisms into organic steel coatings
Avenues of Commercialisation for Nano and Micro technologies (ACNM)
A cross-disciplinary soil-proteomics and modelling approach for predicting switches between hydrophilic and hydrophobic soil surface responses
Improving the efficiency of natural product expression and purification in bacterial strains of pharmaceutical relevance by biomimetic culturing
Production, upscaling and analysis of (mixtures of) novel natural products using a biomimetic culturing approach

Cyhoeddiadau Is-thema Cysylltiedig

2020

Ortiz-Monslave S, Gutterres M, Valente P, Plácido J, Bustamante-López S, Kelly D, Kelly SL. Degradation of a leather-dye by the combination of depolymerised wood-chip biochar adsorption and solid-state fermentation with Trametes villosa SCS-10. Bioresources and Bioprocessing. 2020, https://bioresourcesbioprocessing.springeropen.com/articles/10.1186/s40643-020-00349-z.

Lamb DC, Hargrove TY, Zhao B, Wawrzak Z, Goldstone JV, Nes WD, Kelly SL, Waterman MR, Stegeman JJ, Lepesheva GI. Concerning P450 evolution: structural analyses support bacterial origin of sterol 14α-demethylases. Molecular Biology and Evolution. 2020, doi: https://doi.org/10.1093/molbev/msaa260.

Poloni NM, Carvalho G, Vicentini SNC, Dorigan AF, Maciel JLN, McDonald BA, Moreira SI, Hawkins N, Fraaije BA, Kelly DE, Kelly SL, Ceresini PC. Widespread distribution of resistance to triazole fungicides in Brazilian populations of the wheat blast pathogen. Plant Pathology. 2020, https://doi.org/10.1111/ppa.13288.

Binjubair FA, Parker JE, Warrilow AG, Puri K, Braidley PJ, Tatar E, Kelly SL, Kelly DE, Simons C. Small-Molecule Inhibitors Targeting Sterol 14α-Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against Candida albicans. ChemMedChem. 2020, doi: 10.1002/cmdc.202000250.

Rybak JM, Muñoz JF, Barker S, Parker JE, Esquivel BD, Berkow EL, Lockhart SR, Gade L, Palmer GE, White TC, Kelly SL, Cuomo CA, Rogers PD. Mutations in TAC1B: a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris. mBio. 2020, 11 (3) e00365-20; DOI: 10.1128/mBio.00365-20.

Furukawa T, van Rhijn N, Fraczek M, Gsaller F, Davies E, Carr P, Gago S, Fortune-Grant R, Rahman S, Gilsenan JM, Houlder E, Kowalski CH, Raj S, Paul S, Cook P, Parker JE, Kelly SL, Cramer RA, Latgé J-P, Moye-Rowley S, Bignell E, Bowyer P, Bromley MJ. The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus. Nature Communications. 2020, 427.

Morgan SR, Pilia N, Hewitt M, Moses RL, Moseley R, Lewis PN, Morrison PWJ, Kelly SL, Parker JE, Whitaker D, Quantock AJ, Heard CM. Controlled in vitro delivery of voriconazole and diclofenac to the cornea using contact lenses for the treatment of Acanthamoeba keratitis. International Journal of Pharmaceutics. 2020, https://doi.org/10.1016/j.ijpharm.2020.119102.

2019

Kannan A, Asner SA, Trachsel E, Kelly SL, Parker JE, Sanglard D. Comparative Genomics for the Elucidation of Multidrug Resistance in Candida lusitaniae. mBio. 2019, DOI: 10.1128/mBio.02512-19.

Warrilow AGS, Parker JE, Price CL, Rolley NJ, Nes WD, Kelly DE, Kelly SL. Isavuconazole and voriconazole inhibition of sterol 14α-demethylases (CYP51) from Aspergillus fumigatus and Homo sapiens. International Journal of Antimicrobial Agents. 2019, EPub before print.

Plácido J, Bustamante-López S, Meissner KE, Kelly DE, Kelly SL. NanoRefinery of carbonaceous nanomaterials: Complementing dairy manure gasification and their applications in cellular imaging and heavy metal sensing. Science of The Total Environment. 2019, 689, 10-20.

Plácido J, Bustamante-López S, Meissner KE, Kelly DE, Kelly SL. Multivariate analysis of biochar-derived carbonaceous nanomaterials for detection of heavy metal ions in aqueous systems. Science of The Total Environment. 2019, 688, 751-761.

Lamb DC, Follmer AH, Goldstone JV, Nelson DR, Warrilow AG, Price CL, True MY, Kelly SL, Poulos TL, Stegeman JJ. On the occurrence of cytochrome P450 in viruses. 2019. DOI: 10.1073/pnas.1901080116.

Rybak JM, Ge W, Wiederhold NP, Parker JE, Kelly SL, Rogers PD, Fortwendel JR. Mutations in hmg1, challenging the paradigm of clinical triazole resistance in Aspergillus fumigatus. mBio. 2019, DOI: 10.1128/mBio.00437-19.

Nishimoto AT, Wiederhold NP, Flowers SA, Zhang Q, Kelly SL, Morschhäuser J, Yates CM, Hoekstra WJ, Schotzinger RJ, Garvey EP, Rogers PD. In vitro activities of the novel investigational tetrazoles VT-1161 and VT-1598 compared to the triazole antifungals against azole-resistant strains and clinical isolates of Candida albicans. Antimicrobial Agents and Chemotherapy. 2019, DOI: 10.1128/AAC.00341-19.

Warrilow AG, Nishimoto AT, Parker JE, Price CL, Flowers SA, Kelly DE, Rogers PD, Kelly SL. The evolution of azole resistance in Candida albicans sterol 14α-demethylase (CYP51) through incremental amino acid substitutions. Antimicrobial Agents and Chemotherapy. 2019, EPub before print.

Plácido J, Bustamante-López S, Meissner KE, Kelly DE, Kelly SL. Microalgae biochar-derived carbon dots and their application in heavy metal sensing in aqueous systems. Science of the Total Environment. 2019, 656, 531-539.

Griffiths WJ, Crick PJ, Meljon A, Theofilopoulos S, Abdel-Khalik J, Yutuc E, Parker JE, Kelly DE, Kelly SL, Arenas E, Wang Y. Additional pathways of sterol metabolism: Evidence from analysis of Cyp27a1-/- mouse brain and plasma. Biochimica et biophysica acta. Molecular and Cell Biology of Lipids. 2019, DOI: 10.10.1016/j.bbalip.2018.11.006.

Ahmad S, Joseph L, Parker JE, Asadzadeh M, Kelly SL, Meis JF, Khan Z. ERG6 and ERG2 are major targets conferring reduced susceptibility to amphotericin B in clinical Candida glabrata isolates in Kuwait. Antimicrobial Agents and Chemotherapy. 2019, DOI: 10.1128/AAC.01900-18.

Cancer therapyDyson US Patent App. 15/774,569, 2019

Townsend, R., Van Keulen, G., Desbrow, C., & Godfrey, R. (2020). An investigation of the utility of QuEChERS for extracting acid, base, neutral and amphiphilic species from example environmental and clinical matrices. Analytical Science Advances 1(3):152-160 https://doi.org/10.1002/ansa.202000018 , SU Repository: https://cronfa.swan.ac.uk/Record/cronfa54329

2018

Mejia A, Luna D, Fernandez D, Barrios-Gonzalez J, Gutierrez LH, Reyes AG, Absalon AE, Kelly SL. Improving rifamycin production in Amycolatopsis mediterranei by expressing a Vitreoscilla hemoglobin (vhb) gene fused a cytochrome P450 monooxygenase domain. 3 Biotech. 2018. 8: 456.

Zhou W, Warrilow AGS, Thomas CD, Ramos E, Parker JE, Price CL, Vanderloop BH, Fisher PM, Loftis MD, Kelly DE, Kelly SL, Nes WD. Functional importance for developmental regulation of sterol biosynthesis in Acanthamoeba castellanii. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2018. In Press.

Luna-Tapia A, Willems HM, Parker JE, Tournu H, Barker KS, Nishimoto AT, Rogers PD, Kelly SL, Peters BM, Palmer GE. Loss of Upc2p-inducible ERG3 transcription is sufficient to confer niche-specific azole resistance without compromising Candida albicans pathogenicity. mBio. 2018, 9:e00225-18.

Colley T, Sehra G, Chowdhary A, Alanio A, Kelly SL, Kizawa Y, Armstrong-James D, Fisher MC, Warrilow AGS, Parker JE, Kelly DE, Kimura G, Nishimoto Y, Sunose M, Onions S, Crepin D, Lagasse F, Crittall M, Shannon J, McConville M, King-Underwood J, Naylor A, Bretagne S, Murray J, Ito K, Strong P, Rapeport G. In vitro and in vivo efficacy of a novel and long acting fungicidal azole, PC1244, on Aspergillus fumigatus infection. Antimicrobial Agents and Chemotherapy. 2018, doi: 10.1128/AAC.01941-17

A novel alkaliphilic Streptomyces inhibits ESKAPE pathogens (2018) Luciana Terra, Paul J Dyson, Matthew D Hitchings, Liam Thomas, Alyaa Abdelhameed, Ibrahim M Banat, Salvatore A Gazze, Dušica Vujaklija, Paul D Facey, Lewis W Francis, Gerry A Quinn. Frontiers in Microbiology 9, 2458

Gazze, S., Hallin, I., Quinn, G., Dudley, E., Matthews, G., Rees, P., Van Keulen, G., Doerr, S., & Francis, L. (2018). Organic matter identifies the nano-mechanical properties of native soil aggregates. Nanoscale, 10(2), 520-525. https://doi.org/10.1039/C7NR07070E , SU Repository: https://cronfa.swan.ac.uk/Record/cronfa37598

2017

Sewell TR, Hawkins NJ, Stotz HU, Huang YJ, Kelly SL, Kelly DE, Fraaije B, Fitt BDL. Azole sensitivity in Leptosphaeria pathogens of oilseed rape: the role of lanosterol 14alpha-demethylase. Scientific Reports. 2017, 7:15849.

Butts A, DeJarnette C, Peters TL, Parker JE, Kerns ME, Eberle KE, Kelly SL, Palmer GE. Target abundance-based fitness screening (TAFiS) facilitates rapid identification of target-specific and physiologically active chemical probes. mSphere. 2017, DOI: 10.1128/mSphere.00379-17.

Hull CM, Warrilow AGS, Rolley NJ, Price CL, Donnison IS, Kelly DE, Kelly SL. Co-production of 11alpha-hydroxyprogesterone and ethanol using recombinant yeast expressing fungal steroid hydroxylases. Biotechnol Biofuels. 2017, 10:226.

Lemaire B, Karchner SI, Goldstone JV, Lamb DC, Drazen JC, Rees JF, Hahn ME, Stegeman JJ. Molecular adaptation to high pressure in cytochrome P450 1A and aryl hydrocarbon receptor systems of the deep-sea fish Coryphaenoides armatus. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 2017, EPub ahead of print.

Rybak JM, Dicken CM, Parker JE, Caudle K, Manigaba K, Whaley SG, Nishimoto A, Luna-Tapia A, Roy S, Zhang Q, Barker KS, Palmer GE, Sutter TR, Homayouni R, Wiederhold NP, Kelly SL, Rogers PD. Loss of C-5 sterol desaturase activity results in increased resistance to azole and echinocandin antifungals in a clinical isolate of Candida parapsilosis. Antimicrobial Agents and Chemotherapy. 2017, doi: 10.1128/AAC.00651-17.

Warrilow AGS, Parker JE, Price CL, Garvey EP, Hoekstra WJ, Schotzinger RJ, Wiederhold NP, Nes WD, Kelly DE, Kelly SL. The tetrazole VT-1161 is a potent inhibitor of Trichophyton rubrum through its inhibition of T. rubrum CYP51. Antimicrobial Agents and Chemotherapy. 2017, doi: 10.1128/AAC.00333-17.

Colley T, Alanio A, Kelly SL, Sehra G, Kizawa Y, Warrilow AGS, Parker JE, Kelly DE, Kimura G, Anderson-Dring L, Nakaoki T, Sunose M, Onions S, Crepin D, Lagasse F, Crittall M, Shannon J, Cooke M, Bretagne S, King-Underwood J, Murray J, Ito K, Strong P, Rapeport G. In vitro and in vivo antifungal profile of a novel and long acting inhaled azole, PC945, on Aspergillus fumigatus infection. Antimicrobial Agents and Chemotherapy. 2017, doi:10.1128/AAC.02280-16.

Gene silencing in non‐model insects: Overcoming hurdles using symbiotic bacteria for trauma‐free sustainable delivery of RNA interference: Sustained RNA interference in insects mediated by symbiotic bacteria: Applications as a genetic tool and as a biocide (2017) Miranda Whitten, Paul Dyson. Bioessays 39 (3), 1600247

2016

McCourt P, Liu H-Y, Parker JE, Gallo-Ebert C, Donigan M, Bata A, Giordano C, Kelly SL, Nickels Jr JT. Proper sterol distribution is required for Candida albicans hyphal formation and virulence. G3: Genes, Genomes, Genetics. 2016, doi: 10.1534/g3.116.033969.

Warrilow AG, Price CL, Parker JE, Rolley NJ, Smyrniotis CJ, Hughes DD, Thoss V, Nes WD, Kelly DE, Holman TR, Kelly SL. Azole antifungal sensitivity of sterol 14α-demethylase (CYP51) and CYP5218 from Malassezia globosa. Scientific Reports. 2016, 6, 27690.

Warrilow AG, Parker JE, Price CL, Nes WD, Garvey EP, Hoekstra WJ, Schotzinger RJ, Kelly DE, Kelly SL. The investigational drug VT-1129 is a highly potent inhibitor of Cryptococcus species CYP51 but only weakly inhibits the human enzyme. Antimicrobial Agents and Chemotherapy. 2016. 60(8), 4530-4538.

Lemaire B, Kubota A, O'Meara CM, Lamb DC, Tanguay RL, Goldstone JV, Stegeman JJ. Cytochrome P450 20A1 in zebrafish: cloning, regulation and potential involvement in hyperactivity disorders. Toxicology and Applied Pharmacology. 2016, EPub ahead of print.

Goldstone JV, Sundaramoorthy M, Zhao B, Waterman MR, Stegeman JJ, Lamb DC. Genetic and structural analyses of cytochrome P450 hydroxylases in sex hormone biosynthesis: sequential origin and subsequent coevolution. Molecular Phylogenetics and Evolution. 2016, 94 Part B, 676-687.

Symbiont-mediated RNA interference in insects (2016) Miranda MA Whitten, Paul D Facey, Ricardo Del Sol, Lorena T Fernández-Martínez, Meirwyn C Evans, Jacob J Mitchell, Owen G Bodger, Paul J Dyson. Proceedings of the Royal Society B: Biological Sciences 283 (1825), 20160042

2015

Warrilow AGS, Parker JE, Price CL, Nes WD, Kelly SL, Kelly DE. CYP51-mediated azole resistance in Aspergillus fumigatus: an in vitro biochemical study. Antimicrobial Agents and Chemotherapy. 2015, 59(12), 7771-7778.

Hargrove TY, Wawrzak Z, Lamb DC, Guengerich FP, Lepesheva GI. Structure-functional characterization of cytochrome P450 sterol 14alpha-demethylase (CYP51B) from Aspergillus fumigatus and molecular basis for the development of antifungal drugs. The Journal of Biological Chemistry. 2015, 290(39), 23916-23934.

Berkow El, Manigaba K, Parker JE, Barker KS, Kelly SL, Rogers PD. Multidrug transporters and alterations in sterol biosynthesis contribute to azole antifungal resistance in Candida parapsilosis. Antimicrobial Agents and Chemotherapy. 2015, 59(10), 5942-5950.

Derbyshire MC, Michaelson L, Parker J, Kelly S, Thacker U, Powers SJ, Bailey A, Hammond-Kosack K, Courbot M, Rudd J. Analysis of cytochrome b5 reductase-mediated metabolism in the phytopathogenic fungus Zymoseptoria tritici reveals novel functionalities implicated in virulence. Fungal Genetics and Biology. 2015, 82, 69-84.

Lamb DC, Warrilow AG, Rolley NJ, Parker JE, Nes WD, Smith SN, Kelly DE, Kelly SL. Azole antifungal agents to treat the human pathogens Acanthamoeba castellanii and Acanthamoeba polyphaga through inhibition of sterol 14alpha-demethylase (CYP51). Antimicrobial Agents and Chemotherapy. 2015, 59(8), 4707-4713.

Price CL, Parker JE, Warrilow AGS, Kelly DE, Kelly SL. Azole fungicides - understanding resistance mechanisms in agricultural fungal pathogens. Pest Management Science. 2015, 71(8), 1054-1058.

Price CL, Warrilow AGS, Parker JE, Mullins JGL, Nes WD, Kelly DE, Kelly SL. Novel substrate specificity and temperature sensitive activity of Mycosphaerella graminicola CYP51 (MgCYP51) supported by the native NADPH cytochrome P450 reductase (CPR). Applied and Environmental Microbiology. 2015, 81(10), 3379-3386.

2014

Morrison AM, Goldstone JV, Lamb DC, Kubota A, Lemaire B, Stegeman JJ. Identification, modeling and ligand affinity of early deuterostome CYP51s, and functional characterization of recombinant zebrafish sterol 14alpha-demethylase. Biochimia et biophysica acta. 2014, 1840(6), 1825-1836.

Salvage R, Hull CM, Kelly DE, Kelly SL. Use of 70% alcohol for the routine removal of microbial hard surface bioburden in life science cleanrooms. Future Microbiology. 2014, 9(10), 1123-1130.

Hull CM, Loveridge EJ, Donnison IS, Kelly DE, Kelly SL. Co-production of bioethanol and probiotic yeast biomass from agricultural feedstock: application of the rural biorefinery concept. AMB Express. 2014, 4, Epub.

Hull CM, Loveridge EJ, Rolley NJ, Donnison IS, Kelly SL, Kelly DE. Co-production of ethanol and squalene using a Saccharomyces cerevisiae ERG1 (squalene epoxidase) mutant and agro-industrial feedstock. Biotechnology for Biofuels. 2014, 7, Epub.

Warrilow AGS, Hull CM, Parker JE, Garvey EP, Hoekstra WJ, Moore WR, Schotzinger RJ, Kelly DE, Kelly SL. The clinical candidate VT-1161 is a highly potent inhibitor of Candida albicans CYP51 but fails to bind the human enzyme. Antimicrobial Agents and Chemotherapy. 2014, Epub.

Parker JE, Warrilow AGS, Price CL, Mullins JGL, Kelly DE, Kelly SL. Resistance to antifungals that target CYP51. Journal of Chemical Biology. 2014, 7(4), 143-161.

Warrilow AGS, Hull CM, Rolley NJ, Parker JE, Nes WD, Smith SN, Kelly DE, Kelly SL. Clotrimazole as a potent agent for treating the oomycete fish pathogen Saprolegnia parasitica through inhibition of sterol 14alpha-demethylase (CYP51). Applied and Environmental Microbiology. 2014. 80(19), 6154-6166.

Hawkins NJ, Cools HJ, Sierotzki H, Shaw MW, Knogge W, Kelly SL, Kelly DE, Fraaije BA. Paralog re-emergence: a novel, historically contingent mechanism in the evolution of antimicrobial resistance. Molecular Biology and Evolution. 2014, 31(7), 1793-1802.

Carter HE, Fraaije BA, West JS, Kelly SL, Mehl A, Shaw MW, Cools HJ. Alterations in the predicted regulatory and coding regions of the sterol 14alpha-demethylase gene (CYP51) confer decreased azole sensitivity in the oilseed rape pathogen Pyrenopeziza brassicae. Molecular Plant Pathology 2014, 15(5), 513-522.