Visiting Professors

Professor Graham Mitchell , Visiting Professor of Medical Protozoology

Emailgmitch@essex.ac.uk
Room5.01
Qualifications

BSc, Zoology Honours, University of Exeter 1969

PhD, Faculty of Medicine, University of London 1975

MRCPath,  Royal College of Pathologists  1990

FRCPath, 1996

Research interests


My doctoral and immediate post-doctoral studies hinged on effector mechanisms of functional immunity to malaria in primates and man. These included the first effective immunisation of primates against Plasmodium falciparum, early work on the antigenic variability of merozoites, and on vaccine adjuvants. Later, the general perception that molecular analysis was needed for safe vaccines led me to work on AMA-1. This, as Pk66, was first described by us at Guy’s and is a continuing interest: it remains a malaria vaccine candidate molecule.
Merozoites as immunogens and targets led me into the study of invasion mechanisms. Key work here was to show both redundancy and receptor heterogeneity in the merozoite’s interaction with the red cell. This finding acted as a “unifying hypothesis” for many contending mechanisms. In a combination of ultrastructural and molecular studies I have since focussed on the merozoite’s invasion apparatus, including the genesis of rhoptries, the first demonstration of the acto-myosin motor, and the role in microneme emplacement of the f-MAST microtubule structure (which we also initially described). A great deal of this has been in collaboration with L H Bannister. Latterly the invasion biology work of my lab centred on the phospholipid generation involved in the formation of the nascent parasitophorous vacuole as the merozoite enters the red cell, and especially on analysing the reactants which the merozoite secretes to this end, in collaboration with EDDennis.
The need for new antimalarial drugs has led to our assaying the effetiveness of anti-microbial peptides as antimalarials in vitro, with AJMason. For a number of years my lab was in close collaboration with the Holder and Blackman labs at the National Institute for Medical Research, Mill Hill, collaborations which yielded a huge number of insights into malaria parasite biology, most especially on the sequential processing of merozoite functional surface components.
Since moving to Essex, I have extended my interests to include the biological association of Acanthamoeba and its passenger bacterial pathogens, and have introduced work on anti-microbial peptides in this context and as potential adjuvants to antibiotic efficacy in the face of antibiotic resistance.

Publications

1. Original research papers in peer-reviewed journals
G H Mitchell, G A Butcher and S Cohen (1973).
Isola¬tion of blood-stage merozoites from Plasmodium knowlesi malaria.
International Journal for Parasitology 3: 443-445.

G A Butcher, G H Mitchell and S Cohen (1973). Mechanism of host specificity in malaria infection.
Nature 244: 40-42.

G H Mitchell, G A Butcher and S Cohen (1974).
A merozoite vaccine effective against Plasmodium knowlesi malaria.
Nature 252: 311-313.

S Cohen, G A Butcher and G H Mitchell (1974).
Mechanisms of immunity to malaria.
Bulletin of the World Health Organisation 50: 251-257.

G H Mitchell, G A Butcher and S Cohen (1975).
Merozoite vaccination against Plasmodium knowlesi malaria.
Immunology 29: 397-407.

E D Dennis, G H Mitchell, G A Butcher and S Cohen (1975).
In vitro isolation of Plasmodium knowlesi merozoites using Polycarbonate sieves.
Parasitology 71: 475-581.

L H Bannister, G A Butcher, E D Dennis and G H Mitchell (1975).
Structure and invasive behaviour of Plasmodium knowlesi merozoites in vitro.
Parasitol¬ogy 71: 483-491.

G H Mitchell, G A Butcher, A Voller and S Cohen (1976).
The effect of human immune IgG on the in vitro development of Plasmodium falciparum.
Parasitology 72: 149-162.

G H Mitchell (1977).
Merozoite vaccina¬tion against Plasmodium knowlesi malaria.
Transac¬tions of the Royal Society of Tropical Medicine and Hygiene 71: 281-282.

G H Mitchell, W H G Richards, G A Butcher and S Cohen (1977).
Merozoite vaccination of douroucouli monkeys against falciparum malaria.
Lancet i: 1335-1338.

G H Mitchell, G A Butcher, J Langhorne and S Cohen (1977).
A freeze-dried merozoite vaccine effective against Plasmodium knowlesi malaria.
Clinical and Experimental Immunol¬ogy 28: 276-279.

W H G Richards, G H Mitchell, G A Butcher and S Cohen (1977). Merozoite vaccination of rhesus monkeys against Plasmodium knowlesi malaria; immunity to sporozoite (mosquito-transmitted) challenge.
Parasitology 74: 191-198.

S Cohen, G A Butcher, G H Mitchell, J A Deans and J Langhorne (1977).
Acquired immunity and vaccination in malaria.
American Journal of Tropical Medicine and Hygiene 26: 223-232.

G A Butcher, G H Mitchell and S Cohen (1978).
Antibody mediated mechanisms of immunity to malaria in¬duced by vaccination with Plasmodium knowlesi merozoites.
Immunology 34: 77-86.

G H Mitchell, W H G Richards, A Voller, F M Dietrich and P Dukor (1979).
Nor-MDP, Saponin, corynebacteria and pertussis organisms as immunological adjuvants in experimental malaria vaccination of macaques.
Bulletin of the World Health Organisation 57: S 189-197.

J M Wickham, E D Dennis and G H Mitchell (1980).
Long term culture of a simian malaria parasite (Plasmodium knowlesi) in a semi-automated apparatus.
Transactions of the Royal Society of Tropical Medicine and Hygiene 74: 789-792.

G H Mitchell, S Cohen, C D V Black, A Voller, F M Dietrich and P Dukor (1981).
Novel adjuvants in malaria vaccination.
Transactions of the Royal Society of Tropical Medicine and Hygiene 75: 187-188.

P S Shepherd, P B Burke, A W Thomas, G H Mitchell and S Cohen (1982).
Circulating immune complexes in Plasmodium knowlesi-infected kra and merozoite-vaccinated rhesus monkeys.
Clinical and Experimental Immunology 48: 315-320.


J A Deans, T Alderson, A W Thomas, G H Mitchell, E S Lennox and S Cohen (1982).
Rat monoclonal antibodies which inhibit the in vitro multiplication of Plas¬modium knowlesi.
Clinical and Experimental Immunology 49: 297-309.


A W Thomas, J A Deans, G H Mitchell, T Alderson and S Cohen (1984).
The Fab fragments of monoclonal IgG to a merozoite surface antigen inhibit Plasmodium knowlesi invasion of erythrocytes.
Molecular and Biochemical Parasitology 13: 187-199.

C A Facer and G H Mitchell (1984).
Wr(b) negative erythrocytes are susceptible to invasion by malaria parasites.
Lancet ii: 758-759.

N Wedderburn, G H Mitchell and D R Davies (1985).
Plasmodium brasilianum in the common marmoset Callithrix jacchus.
Parasitology 90: 573-578.

S Sharma, P Svec, G H Mitchell and G N Godson (1985). Diversity of circumsporozoite antigen genes from two strains of the malarial parasite P. knowlesi.
Science 229: 779-782.

L H Bannister, G H Mitchell, G A Butcher and E D Dennis (1986)
Lamellar membranes associated with rhoptries in erythrocytic merozoites of Plasmodium knowlesi: a clue to the mechanism of invasion.
Parasitology 92: 291-303.

L H Bannister and G H Mitchell (1986)
Lipidic vacuoles in Plasmodium knowlesi erythrocytic schizonts.
Journal of Protozoology 33: 271-275.

G H Mitchell, T J Hadley, M H McGinniss, F W Klotz and L H Miller (1986).
Invasion of erythrocytes by Plasmodium falciparum malaria parasites: evidence for receptor heterogeneity and two receptors.
Blood 67: 1519-1521.

L H Bannister, G H Mitchell, G A Butcher, E D Dennis and S Cohen (1986).
Structure and development of the surface coat of Plasmodium knowlesi erythrocytic merozoites.
Tissue and Cell Research 245: 281-290.

G H Mitchell, D A Johnston, B A Naylor, A M Knight and N Wedderburn (1988).
Plasmodium vivax malaria in the common marmoset, Callithrix jacchus: adaptation and host response to infection.
Parasitology 96: 241-250

N Wedderburn, D R Davies, C Desgranges, G H Mitchell and G de The (1988).
Glomerulonephritis associated with concurrent infection of the common marmoset with Plasmodium brasilianum and Epstein-Barr virus.
Journal of Infectious Diseases 158: 789-794

J A Deans, A M Knight, W C Jean, A P Waters, S Cohen, and G H Mitchell (1988).
Vaccination trials in rhesus monkeys with a minor, invariant, Plasmodium knowlesi 66 kilodalton merozoite antigen.
Parasite Immunology 10: 535-552.

L H Bannister and G H Mitchell (1989)
The fine structure of secretion by Plasmodium knowlesi merozoites during red cell invasion.
Journal of Protozoology 36: 278-283

D A Johnston, P G Dockrell, A M Knight, G H Mitchell, B A Naylor, A P Waters, and N Wedderburn (1989)
The marmoset adapted malaria strain MVF1: re-evaluation of parasite identity
Transactions of the Royal Society of Tropical Medicine and Hygiene 83: 863

D A Johnston, A M Knight, B A Naylor, N Wedderburn and G H Mitchell (1990)
Monoclonal antibodies from Epstein-Barr virus-transformed lymphocytes of common marmosets (Callithrix jacchus) immune to malaria
Journal of Immunological Methods 127: 187-195

A P Waters, A W Thomas, J A Deans, G H Mitchell, D E Hudson, L H Miller, T F McCutchan, and S Cohen (1990)
A merozoite receptor protein from P knowlesi is highly conserved and distributed throughout Plasmodium
Journal of Biological Chemistry 265: 17974 - 17979

A P Waters, A W Thomas, G H Mitchell, and T F McCutchan (1991)
Intra-generic conservation and limited inter-strain variation in a protective minor surface antigen of Plasmodium knowlesi merozoites
Molecular and Biochemical Parasitology 44: 141-144

A R Dluzewski, G H Mitchell, P R Fryer, S Griffiths, RJ M Wilson, and W B Gratzer (1992)
Origins of the parasitophorous vacuole membrane of the malaria parasite, Plasmodium falciparum, in human red blood cells
Journal of Cell Science 102: 527-532

M Goodier, M Krause-Jauer, A Sanni, A Massougbodji, B-C Sadeler, G H Mitchell, M Modell, K Eichmann, and J Langhorne (1993)
/ -T cells in the peripheral blood of individuals from an area of holoendemic Plasmodium falciparum transmission. Transactions of the Royal Society of Tropical Medicine and Hygiene 87:692-696

A W Thomas, D Narum, A P Waters, J F Trape, C Rogier, A Goncalves, V Rosario, P Druilhe, G H Mitchell, and E D Dennis (1994)
Aspects of immunity for the AMA-1 family of molecules in human and non-human primate malarias.
Memorias do Instituto Oswaldo Cruz 89 Supp 2: 67-70

L H Bannister, and G H Mitchell (1995)
The role of the cytoskeleton in Plasmodium falciparum merozoite biology: an electron microscopic view.
Annals of Tropical Medicine and Parasitology 89: 105-111

S E Webb, R E Fowler, C O'Shaughnessy, J C Pinder, A R Dluzewski, W B Gratzer, L H Bannister, and G H Mitchell (1996)
Contractile protein system in the asexual stages of the malaria parasite Plasmodium falciparum.
Parasitology 112: 451-458

P A Bejon, L H Bannister, R E Fowler, R E Fookes, S E Webb, A Wright and G H Mitchell (1996)
A role for microtubules in Plasmodium falciparum merozoite invasion
Parasitology 114 1-6

J C Pinder, R.E Fowler, A.R Dluzewski, L.H Bannister, F.M Lavin,. G.H Mitchell, R.J.M Wilson and W.B. Gratzer (1998)
An actomyosin motor in the merozoite of the malaria parasite Plasmodium falciparum: implications for red cell invasion. Journal of Cell Science 111: 1831-1839

R E Fowler, R E Fookes, F M Lavin, L H Bannister, and G H Mitchell (1998)
Microtubules in Plasmodium falciparum merozoites and their importance for invasion of erythrocytes. Parasitology 117: 425-433

R E Fowler, R E Fookes, L H Bannister and G H Mitchell (1998) Malaria, microtubules, and merozoite invasion. Parasitology Today 14: 41 Letter

J M Hopkins, R E Fowler, S Krishna, R J M Wilson, G H Mitchell, & L H Bannister (1999): The plastid in Plasmodium falciparum malaria asexual blood stages: a three dimensional ultrastructural analysis.
Protist 150 283-295

L.H Bannister, J.M.Hopkins, R.E. Fowler, S. Krishna, and G.H.Mitchell (2000)
Ultrastructure of rhoptry development in Plasmodium falciparum erythrocytic
schizonts. Parasitology 121, 273-287

G Margos, I Siden-Kiamos, F E Fowler, T R Gillman, G Lycett, D Vlachou, W Eling, G H Mitchell, and C Louis (2000): Myosin-A expression in ookinete stages of Plasmodium berghei. Molecular and Biochemical Parasitology 111, 465-469

Fowler, RE, Smith, AM, Whitehorn, J, Williams, IT, Bannister, LH, and Mitchell, GH (2001) Microtubule associated motor proteins of Plasmodium falciparum merozoites. Mol.Biochem.Parasitol., 117: 187-200.
Bannister,L.H.; Hopkins,J.M.; Dluzewski,A.R.; Margos,G.; Williams,I.T.; Blackman,M.J.; Kocken,C.H.; Thomas,A.W.; Mitchell,G.H. (2003) Plasmodium falciparum apical membrane antigen 1 (PfAMA-1) is translocated within micronemes along subpellicular microtubules during merozoite development. Journal of Cell Science 116: 3825-3834
J Chaparro-Olaya, A R Dluzewski, G Margos, J M Hopkins, M M Wasserman, G H Mitchell, L H Bannister, and J C Pinder (2003). The multiple myosins of malaria: The smallest malaria myosin, Plasmodium falciparum myosin-B (Pfmyo-B) is expressed in mature schizonts and merozoites. European Journal of Protistology 39: 423-427

G H Mitchell, A W Thomas, G Margos, A R Dluzewski, and L H Bannister (2004)
Apical Membrane Antigen-1 (AMA-1), a major candidate malaria vaccine molecule, mediates the close attachment of invasive merozoites to host red cells. Infection and Immunity 72: 154-158
L H Bannister, J M Hopkins, G Margos, A R Dluzewski, and G H Mitchell (2004) Three-dimensional ultrastructure of the ring stage of Plasmodium falciparum: evidence for export pathways. Microscopy and Microanalysis 10 (special issue: Cellular Biology of Protozoan Parasites) 551-562

Margos G, A R Dluzewski, L H Bannister, J M Hopkins, I T Williams, G H Mitchell (2004)
Correlation of structural development and differential expression of invasion-related molecules in schizonts of Plasmodium falciparum Parasitology 129: 273-287

Harris PK, Yeoh S, Dluzewski AR, O’Donnell RA, Withers-Martinez C, Hackett F, Bannister LH, Mitchell GH, Blackman MJ (2005) Molecular Identification of a malaria merozoite surface sheddase. PLoS Pathogens 1:241-251 e29.

J. Chaparro-Olaya, G. Margos, D. J. Coles, A. R. Dluzewski, G. H. Mitchell, M. M. Wasserman and J. C. Pinder. (2005) Plasmodium falciparum myosins: Transcription and translation during asexual parasite development Cell motility and the Cytoskeleton 60, 200-213.

J. A. Pachebat, M Kadekoppala M Grainger, A R. Dluzewski, R S.Gunaratne, T J Scott-Finnigan, S A Ogun, I T. Ling, L H. Bannister, H M.Taylor, G H. Mitchell, and A A. Holder (2007)
Extensive proteolytic processing of the malaria parasite Merozoite Surface Protein 7 during biosynthesis and parasite release from erythrocytes. Mol.Biochem.Parasitol., 151, 59–69


Yeoh S, O'Donnell RA, Koussis K, Dluzewski AR, Ansell KH, Osborne SA, Hackett F, Withers-Martinez C,
Mitchell GH, Bannister LH, Bryans JS, Kettleborough CA, Blackman MJ. (2007)
Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes. Cell. 131(6):1072-83

Dluzewski AR, Ling IT, Hopkins JM, Grainger M, Margos G, Mitchell GH, Holder AA, Bannister LH. (2008)
Formation of the food vacuole in Plasmodium falciparum: a potential role for the 19 kDa fragment of merozoite surface protein 1 (MSP1(19)). PLoS ONE. 2008 Aug 29;3(8):e3085.


Butcher GA, Mitchell GH, Cohen S 2010) Plasmodium knowlesi infections in a small number of non-immune natural hosts (Macaca fascicularis) and in rhesus monkeys (M. mulatta) Transactions of the Royal society of Tropical Medicine and Hygiene 104 (1) 75-77
Vermeer, L. S., Y. Lan, V. Abbate, E. Ruh, T. T. Bui, L. J. Wilkinson, T. Kanno, E. Jumagulova, J. Kozlowska, J. Patel, C. A. McIntyre, W. Yam, G. Siu, R. Atkinson, J. K. Lam, S. S. Bansal, A. F. Drake, G. H. Mitchell, and A. Mason. 2012. Conformational Flexibility Determines Selectivity and Antibacterial, Antiplasmodial, and Anticancer Potency of Cationic alpha-Helical Peptides. Journal of Biological Chemistry 287:34120-34133
Moon, R. W., J. Hall, F. Rangkuti, Y. S. Ho, N. Almond, G. H. Mitchell, A. Pain, A. A. Holder, and M. J. Blackman. 2013. Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes. Proceedings of the National Academy of Sciences of the United States of America 110:531-536.


2. Original research papers invited in Proceedings and other serials (not all peer-reviewed)

S Cohen, G A Butcher and G H Mitchell (1972).
In vitro studies of malarial antibody.
Basic Research in Malaria: Proceedings of the Helminthological Society of Washington 39: 231-237.

L H Bannister, G A Butcher and G H Mitchell (1977).
Recent advances in understanding the invasion of erythrocytes by merozoites of Plasmodium knowlesi.
Bulletin of the World Health Organisation 55: 163-169

J Langhorne, G A Butcher, G H Mitchell and S Cohen (1979). Preliminary investigations on the role of the spleen in immunity to Plasmodium knowlesi malaria.
In: Tropical Diseases Research Series 1: Role of the spleen in the immunology of parasitic diseases. Schwabe, Basel, pp205-225.

S Cohen, E D Dennis and G H Mitchell (1980).
Isola¬tion and properties of erythrocytic malaria merozoites.
In: Tropical Diseases Research Series 3: The in vitro cultivation of the pathogens of tropi¬cal disease. Schwabe, Basel, pp51-76.

G H Mitchell, S Cohen, C D V Black, A Voller, F M Dietrich and P Dukor (1981)
Novel adjuvants in malaria vaccination.
In: The Host Invader Interplay (Ed. H van den Bossche) Elsevier, Amsterdam, 1981, pp629-632

F M Dietrich, W Sackman, G H Mitchell and A Voller (1983).
Modulation of resistance to infection by synthetic low-molecular-weight compounds endowed with immunostimulatory properties: experimental results and potential role in human medicine.
In: Proceed¬ings of the International Symposium on Chemotherapy and Immunology in the Control of Malaria, Filariasis and Leishmaniasis. (Ed. N Anand and A B Sen) Tata McGraw Hill, New Delhi

S Cohen, J A Deans, G H Mitchell, A W Thomas, A P Waters and T Alderson (1985).
Putative protective antigens of Plasmodium knowlesi bloodstage parasites.
In: Vaccines 1985 (Eds. R A Lerner, R M Channock and F Brown), Cold Spring Harbor, NY, pp19-24.

3. Chapters, Reviews, and Editorials

S Cohen, G A Butcher and G H Mitchell (1977).
Immunization against erythrocytic forms of malaria parasites.
Advances in Experimental Medicine and Biology 93: 89-112.

S Cohen and G H Mitchell (1978).
Prospects for immunization against malaria.
Current Topics in Microbiology and Immunology 80: 97-137.

G H Mitchell (1984).
Host responses to malaria: Im¬munity.
In: Experimental Pharmacology of Antimalaria Drugs Vol. 1 (Eds. W Peters and W H G Richards) Springer-Verlag, Berlin pp101-125.

G H Mitchell (1984). Vaccination against malaria: its plausibility and the present state of research.
Vaccine 2: 115-124.


G H Mitchell (1987).
The comparative immunobiology of Plasmodium: model systems and new technologies in malaria vaccine research.
In: Progress in Veterinary Microbiology and Immunology: 3, Biotechnology and Com¬parative Medicine, (Ed. R Pandey), Karger, Basel, pp112-138.

G H Mitchell and L H Bannister (1988).
Malaria parasite invasion: interactions with the red cell membrane.
Critical Reviews in Oncology and Haematol¬ogy 8: 255-310

G H Mitchell (1988)
Immunization against protozoan disease.
Current Opinion in Infectious Diseases 1: 883-889.

G H Mitchell (1989)
An update on candidate malaria vaccines.
In: Vaccines and vaccination strategies. Symposium of the British Society for Parasitology number 26 (Ed D J McLaren) Parasitology 98: S29-S47.

G H Mitchell (1989)
Immunization against parasitic disease
Current Opinion in Infectious Diseases 2: 765-772

G H Mitchell (1989)
A vaccine for ovine cysticercosis
Vaccine 7: 379 (editorial)

G H Mitchell (1990)
Progress towards malaria vaccination
Current Opinion in Infectious Diseases 3: 387-392

G H Mitchell (1991) Malaria research in Colombia: has a useful malaria vaccine arrived?
Vaccine 9: 219-220 (editorial)

J C Pinder, R E Fowler, L H Bannister, A R Dluzewski, and G H Mitchell (2000)
Motile systems in malaria merozoites: how is the red cell invaded?
Parasitology Today 16, 240-245


L H Bannister, J M Hopkins, R E Fowler, S Krishna, and G H Mitchell (2000)
A brief illusrated guide to the ultrastructure of Plasmodium falciparum asexual blood stages
Parasitology Today 16 427-433

Bannister, L.H. and G.H. Mitchell. (2003).
The ins, outs and roundabouts of malaria.
Trends Parasitol. 19:209-213

R E Fowler, G Margos and G H Mitchell (2003)
The cytoskeleton and motility in Apicomplexan invasion.
Advances in Parasitology 56 213-263

L H Bannister and G H Mitchell (2009) The malaria merozoite, forty years on
Parasitology 136 (12) Special Issue: 1435-1444

4. CD ROMs
DC Warhurst, R Webber, BJ Brabin, JMS Crawley, G Pasvol, and GH Mitchell. (1998) Malaria: Overview in Topics in International Health: Malaria (ed T Beanland) Wellcome Trust, London/ CAB International, Wallingford ISBN 0 85199 243 9
G H Mitchell and G Pasvol. (Advisors)(1998) Malaria: Immunity in Topics in International Health: Malaria (ed T Beanland) Wellcome Trust, London/ CAB International, Wallingford ISBN 0 85199 243 9

G H Mitchell (Advisor) (2001) Malaria: Immunity, ibid (2nd edition), ISBN 0 85199 494 6

G H Mitchell and S Kinyanjui (Advisors) (2007) – ibid (3rd edition) ISBN 978 1 84129 064 5

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