Research Output per year
Paul is a Senior Lecturer of Microbiology at Teesside University in the School of Science, Engineering and Design. His past and current research aims to understand disease processes in numerous infectious diseases including E. coli, Salmonella, Microsporidia and Entamoeba. Paul has a real passion for microbes and actively writes papers, reviews, books chapters, and has acted as Associate Editor for several scientific journals.
He previously lectured at Newcastle University where he also carried out 15 years of research into pathogens that cause enteric disease. He now lectures on a broad range of biological disciplines covering several modules in the Biomedical Science degree including Medical Microbiology, Life Sciences, Biotherapeutics, Bioethics and Communication, Human Diseases and Immunology, Cell Biology and Biological Methods.
Paul is actively involved in promoting links with local schools and colleges through STEMulate and as moderator for Access to HE Diploma certificates delivered through ONE awards. STEMulate is a great way for school students to see what Teesside has to offer and allows students to really get stuck into some experiments!
Paul's research centres around pathogens, how they infect us and how our cells respond to them. He uses a variety of model systems including insect and mammalian cells. Recently, Paul's research has focussed on how protein transporters enable pathogens to steal vital metabolites from hosts such as humans.
Our research: Visualising bugs using High resolution microscopy
Understanding virulence mechanisms is key to combating infection. We use microscopy and molecular biology to try to decode a pathogen's virulence strategy. These mechanisms have evolved and remained hidden for millions of years so it’s a very interesting job to try to uncover the pathogen's secrets in the lab.
We have considerable experience visualising the internal structures of bacteria, mammalian cells and various parasites. Much of this work is published. Some images have won competitions and appeared on several journal and book covers.
Over the years, we have probably captured well over 20,000 images and videos of bugs and cells using a range of microscopes, including Leica, Zeiss confocals and super-resolution, Zeiss apotome, Atomic Force, Scanning electron and Transmission electron microscopes. Below are some of my favourites:
Book and Journal covers
Understanding Microsporidia parasites
Microsporidia are fascinating eukaryotic parasites that infect humans and animals. The infection process starts with a spore which injects the small parasite cell into the larger host cell through a long germination tube. These parasites can only live grow inside host cells so they are obligate intracellular parasites.
Our work with Microsporidia looks at how they steal metabolites from their host. Below you will see a microscopy image of the parasite from the human pathogenic species Trachipleistophora hominis growing inside a Rabbit kidney cell. The parasite appears red as they are stained with antibodies against the parasite's nucleotide transporter protein NTT - which allows them to steal nucleotides from the host cytoplasm - and is the subject of the paper shown below.
Immunofluorescence of Rabbit kidney cell infected with Microsporidia.
Red = parasite membrane transporter. Blue = DNA. Green = parasite organalles called mitosomes.
Our paper on nucleotide stealing in Microsporidia, with the cartoon below showing the complexity of the interaction based on our data.
Visualising Bacterial Effector Proteins inside Host cells
Bacteria such as pathogenic E. coli deliver millions of molcules into the host cell. Here, E. coli are stained blue (DAPI-stained) and can be seen adhering to the outside of the cell. The green and red-labelled antibodies show the E. coli proteins inside the mammalian cell. You can see, there is a hige amount!
The E.coli effector EspF inside a mammalian cell
Here you see the E. coli effector protein EspF (green) labelled with an anti-EspF antibody. The red is the host cytoskeleton labelled with phalloidin-RFP. Blue is DAPI stained DNA. The amount of bacterial effector protein inside the host cell is phenomenal!
Past Research: Invertebrate Blood cells and bacteria
Insect Immune cell cytoskeleton
Insect blood cells are fascinating as they respond to foreign materials by spreading all over them, including glass coverslips! This results in some impressive spreading phenotypes, with lots of filopodia (shown here). This cell was stained with the fungal toxin phalloidin that was bound to a red fluorescent probe
Insect Phagocyte engulfing E. coli
Insect phagocytes are vital components of the insect immune system. Here this cell has ingested over 500 FITC-labelled E. coli! The red label is phalloidin-stained cytoskeleton; green is FITC-labelled E. coli
Insect Phagocyte mopping up E. coli
The insect immune system is not like our own as it does not use antibodies. Instead, the insect relies on blood cells that can eat enormous amounts of bacteria. It also relies on a cell-cell cooperation event called nodulation where the cells get together to suffocate invaders!
My favourite bug: Enteropathogenic E. coli
Scanning electron micrograph of microvilli dissolution by E. coli
E. coli sinking into our gut microvilli. The bacteria has an ingenious way of making the microvilli disappear and we still haven't worked out how it does it.
Effacement of gut microvilli by E. coli
Scanning Electron micrograph. After around 30 min, E. coli causes mass loss of microvilli. Bacteria are pseudo-coloured post-capture so look like Jelly beans!
Pedestal formation by E. coli
Scanning electron Microscopy. The pedestal under the bacterium is due to actin polymerisation in the host cell
- Editorial: Stealing is the deal (2019). Major P, Sendra KM, Dean P, Williams TA, Watson AK Thwaites D, Embley TM, Hirt RP (2019). eLife Digests 19 August 2019.
- Major P, Sendra KM, Dean P, Williams TA, Watson AK Thwaites D, Embley TM, Hirt RP (2019). A new family of cell surface located purine transporters in Microsporidia and related fungal endoparasites. eLife (2019). DOI 10.7554/eLife.47037
- Dean, P, Heunis, T, Harlova, A Trost, M. (2019). Regulation of phagosome functions by post-translational modifications: a new paradigmCurrent Opinions in Chemical Biology (2019). 48:73-80. DOI: 10.1016/j.cbpa.2018.11.001
- Dean P, William T, Major P, Goldberg A, Nakjang S, Watson A, Sendra K, Kozhevnikova E, Kunji E, Lucocq J, Hirt R, Embley M (2018) Ancestral reconstruction of a functional nucleotide ADP/ATP exchanger and its lineage-specific evolution in microsporidia. Nature Commun (2018). 1709 (2018) *Corresponding author DOI: 10.1038/s41467-018-03923-4
- Dean P, Hirt RP, Embley TM (2016) Microsporidia: Why Make Nucleotides if You Can Steal Them? PLOS Pathogens 12(11). *Corresponding author. DOI: 10.1371/journal.ppat.1005870
- Molik S, Goldberg AV, Hacker C, Dean P, Williams T, Nakjang S, Long S, Heinz E, Hirt R, Lucocq J, Embley M, Lill R. (2017). Evolutionary conservation and in vitro reconstruction of microsporidian Fe/S cluster biosynthesis. Nature Commun 4:13932. DOI: 10.1038/ncomms13932
- Gawthorne JA, Audry L, McQuitty C, Dean P, Christie JM, Enninga J, Roe AJ. (2015).Visualizing the Translocation and Localization of Bacterial Type III Effector Proteins by Using a Genetically Encoded Reporter System. Applied and environ. Microbiol. 82 (9), 2700-2708. DOI: 10.1128/aem.03418-15
- Dean P, Quitard S, Bulmer D, Roe AJ, Kenny B. (2015). Cultured enterocytes internalise bacteria across their basolateral surface for, pathogen-inhibitable, trafficking to the apical compartment. Scientific Reports 5, Article number: 17359. DOI: 10.1038/srep17359
- Heinz E, Hacker C, Dean P, Mifsud J, Goldberg AV, Williams TA, Nakjang S, Gregory A, Hirt RP, Lucocq JM, Kunji ERS, Embley TM (2014) Plasma membrane-located purine nucleotide transport proteins are key to host exploitation by microsporidian intracellular parasites. PLOS Pathogens 10(12): e1004547. DOI: 10.1371/journal.ppat.1004547
- Dean P, Major P, Nakjang S, Hirt RP and Embley TM (2014). Transport proteins of parasitic protists and their role in nutrient salvage. Front. Plant Sci. 5:153. *Corresponding author. DOI: 10.3389/fpls.2014.00153
- Dean P and Kenny B (2013). Do Caco-2 subclones provide more appropriate in vitro models for understanding how human enteric pathogens cause disease? Future Microbiology. Vol 8: 701-703. DOI: 10.2217/fmb.13.51
- Dean P*, Quitard S, Young L and Kenny B (2013). Insights into the Pathogenesis of Enteropathogenic E. coli Using an Improved Intestinal Enterocyte Model. PLOS ONE, vol. 8, no. 1, 2013. *Corresponding author. DOI: 10.1371/journal.pone.0055284
- Dean, P. Kenny B. A bacterial encoded protein induces extreme multinucleation and cell-cell internalization in intestinal cells. Tissue barriers 1 (1), e22639. DOI: 10.4161/tisb.22639
- Bulmer DM, Kharraz L, Grant AJ, Dean P, Morgan FJ, Karavolos MH, Doble AC, McGhie EJ, Koronakis V, Daniel RA, Mastroeni P, Khan CM (2012). The bacterial cytoskeleton modulates motility, type 3 secretion, and colonization in Salmonella. PLOS Pathogens. vol 8 p. doi:10.1371. DOI: 10.1371/journal.ppat.1002500
- Dean P* (2011). Functional domains and motifs of bacterial type III effector proteins and their roles in infection. FEMS Microbio. Rev. 35(6):1100-1125.*Corresponding and sole author. Article cited over 200 times (2017).DOI: 10.1111/j.1574-6976.2011.00271.x
- Dean P*, Kenny B (2011). Cell-surface nucleolin is sequestered into EPEC microcolonies and may play a role during infection. Microbiology. vol 157 p. 1761-7. *Corresponding author. DOI: 10.1099/mic.0.047506-
- Ruchaud-Sparagano M-H, Muhlen S, Dean P, Kenny B. (2011). The Enteropathogenic E. coli (EPEC) Tir Effector Inhibits NF-kB Activity by Targeting TNFa Receptor-Associated Factors. PLOS Pathogens. vol 7 p. doi:10.1371/. DOI: 10.1371/journal.ppat.1002414
- Dean P*, Muehlen S, Quitard S, Kenny B (2010). The bacterial effectors EspG and EspG2 induce a destructive calpain activity that is kept in check by the co-delivered Tir effector. Cell. Microbiol. vol 12 p. 1308-21. *Corresponding author. DOI: 10.1111/j.1462-5822.2010.01469.x
- Holmes A, Muehlen S, Roe AJ, Dean P* (2010). The EspF effector, a bacterial pathogen's Swiss army knife. Infect. Immun. vol 78 p. 4445-53 *Corresponding author. DOI:10.1128/iai.00635-10
- Dean P*, Scott JA, Knox AA, Quitard S, Watkins NJ, Kenny B (2010). The enteropathogenic E. coli effector EspF targets and disrupts the nucleolus by a process regulated by mitochondrial dysfunction. PLOS Pathogens. 6(6):e1000961. *Corresponding author. DOI: 10.1371/journal.ppat.1000961
- Dean P*, Kenny B (2009). The effector repertoire of enteropathogenic E. coli: ganging up on the host cell. Curr. Opin. Microbiol. 12(1):101-9. *Corresponding author. DOI: 10.1016/j.mib.2008.11.006
- Iguchi A, Thomson NR, Ogura Y, Saunders D, Ooka T, Henderson IR, Harris D, Asadulghani M, Kurokawa K, Dean P, Kenny B, Quail MA, Thurston S, Dougan G, Hayashi T, Parkhill J, Frankel G (2009). Complete genome sequence and comparative genome analysis of enteropathogenic Escherichia coli O127:H6 strain E2348/69. J. Bacteriol. 191(1):347-54.DOI: 10.1128/jb.01238-08
- Quitard S, Dean P, Maresca M, Kenny B (2006). The enteropathogenic Escherichia coli EspF effector molecule inhibits PI-3 kinase-mediated uptake independently of mitochondrial targeting. Cell. Microbiol. 8(6):972-81. DOI: 10.1111/j.1462-5822.2005.00680.x
- Dean P, Maresca M, Schüller S, Phillips AD, Kenny B (2006). Potent diarrheagenic mechanism mediated by the cooperative action of three enteropathogenic Escherichia coli-injected effector proteins. PNAS. 103(6):1876-81. DOI: 10.1073/pnas.0509451103
- Maresca M, Miller D, Quitard S, Dean P, Kenny B (2005). Enteropathogenic Escherichia coli (EPEC) effector-mediated suppression of antimicrobial nitric oxide production in a small intestinal epithelial model system. Cell. Microbiol. 7(12):1749-62. DOI: 10.1111/j.1462-5822.2005.00587.x
- Dean P, Maresca M, Kenny B (2005). EPEC's weapons of mass subversion. Curr. Opin. Microbiol. 8(1):28-34. DOI: 10.1016/j.mib.2004.12.010
- Dean P, Potter U, Richards EH, Edwards JP, Charnley AK, Reynolds SE (2004). Hyperphagocytic haemocytes in Manduca sexta. J. Insect Physiol. 50(11):1027-36.
- Dean P, Kenny B (2004). Intestinal barrier dysfunction by enteropathogenic Escherichia coli is mediated by two effector molecules and a bacterial surface protein. Mol Microbiol. 54(3):665-75. DOI: 10.1111/j.1365-2958.2004.04308.x
- Au C, Dean P, Reynolds SE, ffrench-Constant RH (2004). Effect of the insect pathogenic bacterium Photorhabdus on insect phagocytes. Cell. Microbiol. 6(1):89-95.
- Dean P*, Richards EH, Edwards JP, Reynolds SE, Charnley K (2004). Microbial infection causes the appearance of hemocytes with extreme spreading ability in monolayers of the tobacco hornworm Manduca sexta. Dev. Comp. Immunol. (7-8):689-700. *Corresponding author
- Bundey S, Raymond S, Dean P, Roberts SK, Dillon RJ, Charnley AK (2003). Eicosanoid involvement in the regulation of behavioral fever in the desert locust, Schistocerca gregaria. Arch. Insect Biochem. Physiol. 52(4):183-92.
- Dean P*, Gadsden JC, Richards EH, Edwards JP, Keith Charnley A, Reynolds SE (2002). Modulation by eicosanoid biosynthesis inhibitors of immune responses by the insect Manduca sexta to the pathogenic fungus Metarhizium anisopliae. J. Invertebr. Pathol. Feb; 79(2):93-101. *Corresponding author
- Silva CP, Waterfield NR, Daborn PJ, Dean P, Chilver T, Au CP, Sharma S, Potter U, Reynolds SE, ffrench-Constant RH (2002). Bacterial infection of a model insect: Photorhabdus luminescens and Manduca sexta. Cell. Microbiol. 4(6):329-39.
- Xia Y, Dean P, Judge AJ, Gillespie JP, Clarkson JM, Charnley AK (2000). Acid phosphatases in the haemolymph of the desert locust, Schistocerca gregaria, infected with the entomopathogenic fungus Metarhizium anisopliae. J. Insect Physiol. Sep 1; 46(9):1249-1257.
- Dean P. Cell of the month: An insect blood cell engulfing bacteria. Nat Cell Biol. (2003) Nov; 5 (11):957.
PLOS One - Editorial Board Member
Associate Editor - JBM
Editor Frontiers in Microbiology
Primary Editor - Access Microbiology
Review Editor - JMM
Moderator, Access to HE Diploma - ONE AWARDS
A new family of cell surface located purine transporters in Microsporidia and related fungal endoparasitesMajor, P., Sendra, K. M., Dean, P., Williams, T. A., Watson, A. K., Thwaites, D. T., Embley, T. M. & Hirt, R. P., 29 Jul 2019, In : eLife. 8, e47037.
Research output: Contribution to journal › Article
Research output: Contribution to journal › Article
Stealing is the Deal: Parasites that grow within animal cells use a family of transport proteins to take nucleotides, the building blocks of DNA, from their hosts.Major, P., Sendra, K., Dean, P., Williams, T. A., Watson, A. K., Thwaites, D. T., Embley, T. M. & Hirt, R. P., 19 Aug 2019, In : eLife.
Research output: Contribution to journal › Comment/debate
Transporter gene acquisition and innovation in the evolution of Microsporidia intracellular parasitesDean, P., Sendra, K. M., Williams, T. A., Watson, A. K., Major, P., Nakjang, S., Kozhevnikova, E., Goldberg, A. V., Kunji, E. R. S., Hirt, R. P. & Embley, T. M., 27 Apr 2018, In : Nature Communications. 9, 1
Research output: Contribution to journal › Article
Evolutionary conservation and in vitro reconstitution of microsporidian iron–sulfur cluster biosynthesisFreibert, S., Goldberg, A. V., Hacker, C., Molik, S., Dean, P., Williams, T. A., Nakjang, S., Long, S., Sendra, K., Bill, E., Heinz, E., Hirt, R. P., Lucocq, J. M., Embley, T. M. & Lill, R., 4 Jan 2017, In : Nature Communications. 8, p. 13932
Research output: Contribution to journal › Article