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Professor Derek Nolan
Professor In, Biochemistry

Biography

I have worked on African trypanosomes, which cause human sleeping sickness, for twenty years. As a PhD student I investigated the bioenergetics of T. brucei in Paul Voorheis' laboratory at Trinity College Dublin. Subsequently, I moved to Brussels in 1992, as an EMBO fellow, to join the group of Etienne Pays to study the expression and function of surface proteins in trypanosomes. In 1994 I was awarded a Marie Curie fellowship and focused on the problem of endocytosis in trypanosmes. Trypanosomes are absolutely dependent on their hosts for a supply of iron and lipoproteins and this traffic is highly polarized and extremely rapid in bloodstream forms of the parasite. In the summer of 2001 I was awarded a Senior Fellowship by the Trust to characterize proteins from the flagellar pocket and endocytic pathway in African trypanosomes. These parasitic protozoans cause sleeping sickness in humans and related diseases in domestic animals. Human sleeping sickness is invariably fatal unless treated. Of the four drugs currently employed to treat infections, resistance to two has emerged and the drug of choice, suramin, is suitable only in early stages. Trypanosomiasis is also considered one of the greatest health constraint to livestock productivity in sub-Saharan Africa with costs ranging between $2 and $5 billion annually. African trypanosomes are clearly a global health issue and are an enormous medical, veterinary and economic burden on some of the poorest regions on earth. Apart from their utilitarian interest, trypanosomes have proved to have great intrinsic scientific interest. These unicellular eukaryotes have evolved very differently from the better studied organisms, e.g. bacteria, yeast and metazoans, on which the foundations of biology have been built. Some of the most basic cellular and genetic pathways have developed very differently in trypanosomes but other processes first described and characterized in trypanosomes are now known to be important in mammalian cells. From the nucleus to the plasma membrane trypanosomes have provided fascinating insights including unusual genome organisation, pol I transcription of coding genes, expression sites and novel nuclear substructures, RNA editing, mitochondrial repression/activation, compartmentalization of glycolysis, GPI anchors, unusual organisation of surface proteins and the endocytic pathway, polarized cytoskeletons, golgi duplication and many other phenomena. By any criterion, whether biochemical, molecular or cellular, trypanosomes have more than punched their weight in terms of a contribution to our understanding of eukaryotic biology. osomes and returned to Trinity College Dublin at the end of 2001

Publications and Further Research Outputs

Peer-Reviewed Publications

Fitzgerald, H.K.; O'Rourke, S.A.; Desmond, E.; Neto, N.G.B.; Monaghan, M.G.; Tosetto, M.; Doherty, J.; Ryan, E.J.; Doherty, G.A.; Nolan, D.P.; Fletcher, J.M.; Dunne, A, The Trypanosoma brucei-Derived Ketoacids, Indole Pyruvate and Hydroxyphenylpyruvate, Induce HO-1 Expression and Suppress Inflammatory Responses in Human Dendritic Cells, Antioxidants, 11, 2022, p164- Journal Article, 2022 DOI

Diskin, C. and Corcoran, S.E. and Tyrrell, V.J. and McGettrick, A.F. and Zaslona, Z. and O'Donnell, V.B. and Nolan, D.P. and O'Neill, L.A.J., The Trypanosome-Derived Metabolite Indole-3-Pyruvate Inhibits Prostaglandin Production in Macrophages by Targeting COX2, Journal of immunology (Baltimore, Md. : 1950), 207, (10), 2021, p2551-2560 Journal Article, 2021 DOI

Pays E, Nolan DP., Genetic and immunological basis of human African trypanosomiasis., Current opinion in immunology, 72, 2021, p13-20 Journal Article, 2021 DOI

Hayes P., Fergus C., Ghanim M., Cirzi C., Burtnyak L., McGrenaghan C.J., Tuorto F., Nolan D.P., Kelly V.P., Queuine micronutrient deficiency promotes warburg metabolism and reversal of the mitochondrial ATP synthase in hela cells, Nutrients, 12, (3), 2020 Journal Article, 2020 TARA - Full Text DOI

Lecordier L, Uzureau S, Vanwalleghem G, Deleu M, Crowet JM, Barry P, Moran B, Voorheis P, Dumitru AC, Yamaryo-Botté Y, Dieu M, Tebabi P, Vanhollebeke B, Lins L, Botté CY, Alsteens D, Dufrêne Y, Pérez-Morga D, Nolan DP, Pays E., The Trypanosoma Brucei KIFC1 Kinesin Ensures the Fast Antibody Clearance Required for Parasite Infectivity., iScience, 23, (9), 2020, p101476 Journal Article, 2020 DOI

Campbell NK, Williams DG, Fitzgerald HK, Barry PJ, Cunningham CC, Nolan DP, Dunne A., Trypanosoma brucei Secreted Aromatic Ketoacids Activate the Nrf2/HO-1 Pathway and Suppress Pro-inflammatory Responses in Primary Murine Glia and Macrophages , Frontiers in Immunology-Microbial Immunology, 11, 2019 Journal Article, 2019

Terry K. Smith, Frédéric Bringaud, Derek P. Nolan, Luisa M. Figueiredo, Metabolic reprogramming during the Trypanosoma brucei life cycle, F1000Research, 2017, p683- Journal Article, 2017 TARA - Full Text

Doherty W, Adler N, Knox A, Nolan D, McGouran J, Nikalje A.P, Lokwani D, Sarkate A, Evans P, Synthesis and Evaluation of 1,2,3-Triazole-Containing Vinyl and Allyl Sulfones as Anti-Trypanosomal Agents, European Journal of Organic Chemistry, 2017, (1), 2017, p175 - 185 Journal Article, 2017 URL TARA - Full Text DOI

McGettrick AF, Corcoran SE, Barry PJG, McFarland J, Curtis AM, Franklin E, Corr SC, Mok KH, Cummins EP, Taylor CT, O'Neill LAJ, Nolan DP, The Trypanosoma brucei metabolite indolepyruvate decreases HIF-1 and glycolysis in macrophages as a mechanism of innate immune evasion, Proceedings of the National Academy of Sciences, U.S.A., 113, (48), 2016, pE7778 - E7787 Journal Article, 2016 URL

McGettrick AF, Corcoran SE, Barry PJ, McFarland J, Crès C, Curtis AM, Franklin E, Corr SC, Mok KH, Cummins EP, Taylor CT, O'Neill LA, Nolan DP, Trypanosoma brucei metabolite indolepyruvate decreases HIF-1α and glycolysis in macrophages as a mechanism of innate immune evasion., Proc Natl Acad Sci U S A. , 113, (48), 2016, E7778-E7787 Journal Article, 2016 DOI

Cloonan SM, Elmes RB, Erby M, Bright SA, Poynton FE, Nolan DE, Quinn SJ, Gunnlaugsson T, Williams DC, Detailed Biological Profiling of a Photoactivated and Apoptosis Inducing pdppz Ruthenium(II) Polypyridyl Complex in Cancer Cells., Journal of medicinal chemistry, 58, (11), 2015, p4494-505 Journal Article, 2015 DOI

Cloonan S.M, Elmes R.B.P, Erby M, Bright S.A, Poynton F.E, Nolan D.E, Quinn S.J, Gunnlaugsson T, Williams D.C, Detailed Biological Profiling of a Photoactivated and Apoptosis Inducing pdppz Ruthenium(II) Polypyridyl Complex in Cancer Cells, Journal of Medicinal Chemistry, 58, (11), 2015, p4494 - 4505 Journal Article, 2015 DOI URL

Vanwalleghem G, Fontaine F, Lecordier L, Tebabi P, Klewe K, Nolan DP, Yamaryo-Botté Y, Botté C, Kremer A, Burkard GS, Rassow J, Roditi I, Pérez-Morga D, Pays E.(, Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1., Nature Communications, 6, 2015, p8078 - 8088 Journal Article, 2015 URL TARA - Full Text

Shameer S, Logan-Klumpler FJ, Vinson F, Cottret L, Merlet B, Achcar F, Boshart M, Berriman M, Breitling R, Bringaud F, Bütikofer P, Cattanach AM, Bannerman-Chukualim B, Creek DJ, Crouch K, de Koning HP, Denise H, Ebikeme C, Fairlamb AH, Ferguson MA, Ginger ML, Hertz-Fowler C, Kerkhoven EJ, Mäser P, Michels PA, Nayak A, Nes DW, Nolan DP, Olsen C, Silva-Franco F, Smith TK, Taylor MC, Tielens AG, Urbaniak MD, van Hellemond JJ, Vincent IM, Wilkinson SR, Wyllie S, Opperdoes FR, Barrett MP, Jourdan F., TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei., Nucleic Acids Research, 43, 2015, p637 - 644 Journal Article, 2015 TARA - Full Text

Lecordier L, Uzureau1 P, Tebabi1 P, Pérez-Morga1 D, Nolan DP , Schumann Burkard G, Roditi I and Epays E , Identification of Trypanosoma brucei components involved in trypanolysis by normal human serum. , Molecular Microbiology, 94, 2014, p625 - 636 Journal Article, 2014

Doherty W, James J, Evans P, Martin L, Adler N, Nolan D, Knox A. , Preparation, anti-trypanosomal activity and localisation of a series of dipeptide-based vinyl sulfones., Organic & Biomolecular Chemistry, 12, (38), 2014, p12(38):756 - 7571 Journal Article, 2014

Uzureau, P., Uzureau, S., Lecordier, L., Fontaine, F., Tebabi, P., Homblé, F., Grélard, A., Zhendre, V., Nolan, D.P., Lins, L., Crowet, J.-M., Pays, A., Felu, C., Poelvoorde, P., Vanhollebeke, B., Moestrup, S.K., LyngsÃ", J., Pedersen, J.S., Mottram, J.C., Dufourc, E.J., Pérez-Morga, D., Pays, E., Mechanism of Trypanosoma brucei gambiense resistance to human serum, Nature, 501, (7467), 2013, p430-434 Journal Article, 2013 DOI

Greene, L.M., Nolan, D.P., Regan-Komito, D., Campiani, G., Williams, D.C., Zisterer, D.M., Inhibition of late-stage autophagy synergistically enhances pyrrolo-1,5-benzoxazepine-6-induced apoptotic cell death in human colon cancer cells, International Journal of Oncology, 43, (3), 2013, p927-935 Journal Article, 2013 DOI

Dunny E, Doherty W, Evans P, Malthouse JP, Nolan D, Knox AJ., Vinyl sulfone-based peptidomimetics as anti-trypanosomal agents: design, synthesis, biological and computational evaluation., Journal of Medicinal Chemistry, 56, (17), 2013, p6638 - 6650 Journal Article, 2013

Woods, K, a'Bhaird, NN, Dooley, C, Perez-Morga, D, Nolan, DP, Identification and Characterization of a Stage Specific Membrane Protein Involved in Flagellar Attachment in Trypanosoma brucei, PLOS ONE, 8, (1), 2013, e52846- Journal Article, 2013 TARA - Full Text DOI

Greene, LM, O'Boyle, NM, Nolan, DP, Meegan, MJ, Zisterer, DM, The vascular targeting agent Combretastatin-A4 directly induces autophagy in adenocarcinoma-derived colon cancer cells, BIOCHEMICAL PHARMACOLOGY, 84, (5), 2012, p612-624 Journal Article, 2012 DOI

Diana Spitznagel, John F. O'Rourke, Neal Leddy, Orla Hanrahan, Derek P. Nolan, Identification and Characterization of an Unusual Class I Myosin Involved in Vesicle Traffic in Trypanosoma brucei, PLoS ONE, 5, (8), 2010, pe12282 Journal Article, 2010 TARA - Full Text

Diana Spitznagel, Charles Ebikeme, Marc Biran, Nóirín Nic a' Bháird, Frédéric Bringaud, Gary T. M. Henehan and Derek P. Nolan, Alanine aminotransferase of Trypanosoma brucei- a key role in proline metabolism in procyclic life forms, FEBS Journal, 276, (23), 2009, p7187 - 7199 Journal Article, 2009 DOI

Derek P. Nolan and Jose A. Garcia-Salcedo, Loss of actin does not affect export of newly synthesized proteins to the surface of Trypanosoma brucei, Molecular and Biochemical Parasitology, 157, (2), 2008, p233-235 Journal Article, 2008 DOI

Coustou V, Brian M, Guegan F, Riviere L, Plazolles N, Nolan D, Barrett MP, Franconi JM, Bringaud F., Glucose-induced Remodeling of Intermediary and Energy Metabolism in Procyclic Trypanosoma brucei, The Journal of Biological Chemistry, 283, (24), 2008, p16342-16354 Journal Article, 2008 DOI

Alison E. Adams, Orla Hanrahan, Derek N. Nolan, H. Paul Voorheis, Padraic Fallon and Richard K. Porter, Images of mitochondrial UCP 1 in mouse thymocytes using confocal microscopy , Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1777, (2), 2008, p115 - 117 Journal Article, 2008 TARA - Full Text DOI

Patrick Guirnalda, Noel B. Murphy, Derek Nolan and Samuel J. Black, Anti-Trypanosoma brucei activity in Cape buffalo serum during the cryptic phase of parasitemia is mediated by antibodies, International Journal for Parasitology, 37, (12), 2007, p1391-1399 Journal Article, 2007 DOI

Pays E, Vanhollebeke B, Vanhamme L, Patriaux-Hanocq F, Nolan DP, Perez-Morga D, The trypanolytic factor of human serum, Nature Reviews Microbiology, 4, (6), 2006, p477 - 486 Journal Article, 2006

Nolan, D.P., Jackson, D.G., Biggs, M.J., Brabazon, E.D., Pays, A., Van Laethem, F., Paturiaux-Hanocq, F., (...), Pays, E., Erratum: Characterization of a novel alanine-rich protein located in surface microdomains in Trypanosoma, brucei (Journal of Biological Chemistry (2000) 275 (4072-4080)) , 2005, - 31340 Miscellaneous, 2005

Rubotham, J., Woods, K., Garcia-Salcedo, J.A., Pays, E. and Nolan, D.P., Characterization of two protein disulphide iosmerases from the endocytic pathway of Trypanosoma brucei, Journal of Biological Chemistry, 280, 2005, p10410 - 10418 Journal Article, 2005 DOI TARA - Full Text

Pérez-Morga, D., Vanhollebeke, B., Paturiaux-Hanocq, F., Nolan, D.P., Lins, L., Homblé, F., Vanhamme, L., Tebabi, P., Pays, A., Poelvoorde, P., Jacquet, A., Brasseur, R., Pays, E., Microbiology: Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes, Science, 309, (5733), 2005, p469-472 Journal Article, 2005

Perez-Morga D., Vanhollebeke B., Paturiaux-Hanocq F., Nolan D.P., Lins L., Homble F., Vanhamme L., Tebabi P., Pays A., Poelvoorde P., Jacquet A., Brasseur R., Pays E., Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes, Science, 309, 2005, p469 - 472 Journal Article, 2005 DOI TARA - Full Text

Rubotham, J., Woods, K., Garcia-Salcedo, J.A., Pays, E., Nolan, D.P., Characterization of two protein disulfide isomerases from the endocytic pathway of bloodstream forms of Trypanosoma brucei, Journal of Biological Chemistry, 280, (11), 2005, p10410-10418 Journal Article, 2005

García-Salcedo J.A., Perez-Morga, D., Gijón P., Dilbeek, V., Pays, E. and Nolan, D.P., A differential role for actin in the life cycle of T. brucei., EMBO Journal, 25, 2004, p780 - 789 Journal Article, 2004 DOI TARA - Full Text

García-Salcedo, J.A., Pérez-Morga, D., Gijón, P., Dilbeck, V., Pays, E., Nolan, D.P., A differential role for actin during the life cycle of Trypanosoma brucei, EMBO Journal, 23, (4), 2004, p780-789 Journal Article, 2004

Communication in trypanosomatids in, editor(s)Maudlin, I., Holmes, P.H. and Miles M.A. , Trypanosomiasis and Leishmaniasis, biology and control, Oxford, CAB International, 2003, pp59 - 75, [Nolan, D.P., Garcia Salcedo, J.-A., Vanhamme, L., and Pays, E.] Book Chapter, 2003

Novel approaches for vaccine development against trypanosomiasis in Africa in, editor(s)Serageldin I. And Persley, G.J. , "Biotechonologyand sustainable development: voices of the south and north" Biotechnologyin agriculture series No 26, Oxford, CABInternational, 2003, pp173 - 185, [Murphy, N.B., Nolan, D. and Black, S.J.] Book Chapter, 2003

Vanhamme, L, Paturiaux-Hanocq F., Poelvoorde, P., Nolan, DP, Lins, L, Van den Abbeele, J, Pays, A, Tebabi, P., Xong, HV, Jacquet, A, Moguilevsky, N, Dieu, M, Kane, JP, De Baetselier, P., Brasseur R & Pays, Apolipoprotein L-I is the trypanosome lytic factor of human serum, Nature, 422, 2003, p83 - 87 Journal Article, 2003

García-Salcedo J.A., Gijón P., Nolan, D.P., Tebabi, P. and Pays, E., The histone ADP-ribosyl transferase activity of a trypanosomal SIR2 homologue plays a role in DNA repair, EMBO J., 22, 2003, p5851 - 5862 Journal Article, 2003

García-Salcedo, J.A., Gijón, P., Nolan, D.P., Tebabi, P., Pays, E., A chromosomal SIR2 homologue with both histone NAD-dependent ADP-ribosyltransferase and deacetylase activities is involved in DNA repair in Trypanosoma brucei, EMBO Journal, 22, (21), 2003, p5851-5862 Journal Article, 2003

Garcia-Salcedo, J.A., Nolan, D.P., Gijon-Martin, P., Gomez, J., and Pays, E., A protein kinase specifically associated with proliferative forms of Trypanosoma brucei is functionally related to a yeast kinase involved in the co-ordination of cell shape and division, Mol. Microbiol, 45, 2002, p307 - 319 Journal Article, 2002

Towards a trypanosoiasis vaccine in, editor(s)Seed, R. & Black, S.J. , World Class Parasites Volume 1: The African Trypanosomes, Kluwer Academic Publishers, 2001, pp159 - 174, [Black, S.J., Murphy, N.B. and Nolan, D.P.] Book Chapter, 2001

Pays, E. Lips, S., Nolan, D., Vanhamme, L., and Pérez-Morga D., The VSG expression site of Trypanosoma brucei: multipurpose tools for the adaptation of the parasite to various mammalian hosts, Mol. Biochem. Parasitol., 114, 2001, p1 - 16 Journal Article, 2001

Endocytosis of macromolecules by African trypanosomes in, editor(s)Seed, R. & Black, S.J. , World Class Parasites Volume 1: The African Trypanosomes, Kluwer Academic Publishers, 2001, pp127 - 141, [Nolan, DP, Garcia-Salcedo, J.A., Geuskens, M., Salmon, D., Paturiaux-Hanocq, F., Pays,A., Tebabi, P. and Pays, E.] Book Chapter, 2001

) Endocytosis of macromolecules by African trypanosomes in, editor(s)Eds. Seed, R. & Black, S.J. (Kluwer Academic Publishers) , "World Class Parasites Volume 1: The African Trypanosomes", (Kluwer Academic Publishers) , 2001, pp127 - 141, [Nolan, DP, Garcia-Salcedo, J.A., Geuskens, M., Salmon, D., Paturiaux-Hanocq, F., Pays, A., Tebabi, P. and Pays, E. ] Book Chapter, 2001

Black, S.J., N. Murphy and D. Nolan, Innate and acquired control of trypanosomiasis in Cape buffalo, Int. J. Parasitol., 31, 2001, p562 - 565 Journal Article, 2001

Nolan, D. & Voorheis, H. P., Factors that determine the plasma membrane potential in bloodstream forms of Trypanosoma brucei, European Journal of Biochemistry, 267, (15), 2000, p4615 - 4623 Journal Article, 2000 DOI

NOLAN, DP, JACKSON, DG, BIGGS, MJ, BRABAZON, ED, PAYS, A, VAN LAETHEM, F, PATURIAUX-HANOCQ, F, ELLIOT, JF, VOORHEIS, HP, PAYS, E, CHARACTERIZATION OF A NOVEL ALANINE-RICH PROTEIN LOCATED IN SURFACE MICRODOMAINS IN TRYPANOSOMA BRUCEI, JOURNAL OF BIOLOGICAL CHEMISTRY, 275, 2000, p4072 - 4080 Journal Article, 2000

Redpath MB, Windle H, Nolan D, Pays E, Voorheis HP, Carrington M, ESAG11, a new VSG expression site-associated gene from Trypanosoma brucei., Molecular and biochemical parasitology, 111, (1), 2000, p223-228 Journal Article, 2000 DOI

Nolan, D.P., Rolin, S., Rodriguez, J. R., Van Den Abbeele, J. and Pays, E., Slender and stumpy bloodstream forms of Trypanosoma brucei display a differential response to extracellular acidic and proteolytic stress, Eur. J. Biochem., 267, 2000, p18 - 27 Journal Article, 2000

NOLAN, DP, VOORHEIS, HP, HYDROGEN ION GRADIENTS ACROSS THE MITOCHONDRIAL, ENDOSOMAL AND PLASMA MEMBRANES IN BLOODSTREAM FORMS OF TRYPANOSOMA BRUCEI - SOLVING THE THREE-COMPARTMENT PROBLEM, EUROPEAN JOURNAL OF BIOCHEMISTRY, 267, 2000, p4601 - 4614 Journal Article, 2000

NOLAN, DP, VOORHEIS, HP, FACTORS THAT DETERMINE THE PLASMA-MEMBRANE POTENTIAL IN BLOODSTREAM FORMS OF TRYPANOSOMA BRUCEI, EUROPEAN JOURNAL OF BIOCHEMISTRY, 267, 2000, p4615 - 4623 Journal Article, 2000

Nolan, D.P., Jackson, D.G., Biggs, M.J., Brabazon, E.D., Pays, A., Van Laethem, F., Paturiaux-Hanocq, F., (...), Pays, E., Characterization of a novel alanine-rich protein located in surface microdomains in Trypanosoma brucei , Journal of Biological Chemistry, 275, (6), 2000, p4072 - 4080 Journal Article, 2000 DOI

Radwanska, M., Magez, S., Dumont, N., Pays, A., Nolan, D., and Pays, E., Antibodies raised against the flagellar pocket fraction of Trypanosoma brucei preferentially recognize HSP60 in a cDNA expression library, Parasit. Immunol, 22, 2000, p639 - 650 Journal Article, 2000

Redpath, M.B., Windle, H., Nolan, D., Pays, E., Voorheis, H.P., & Carrington, M., ESAG11, a new VSG expression site-associated gene from Trypanosoma brucei, Mol. Biochem. Parasitol., 111, 2000, p223 - 228 Journal Article, 2000

Paturiaux-Hanocq, F., Hanocq-Quertier, J., Cardoso de Almeida, L., Nolan, D.P., Pays, A., Vanhamme, L., Van den Abbeele, J., Carrington, M. and Pays, E., A role for the dynamic acylation of a cluster of cysteine residues in regulating the activity of the glycosylphosphatidylinositol-specific phospholipase C of Trypanosoma brucei, J. Biol. Chem., 275, 2000, p12147 - 12155 Journal Article, 2000

Nolan, D. & Voorheis, H. P., Hydrogen ion gradients across the mitochondrial, endosomal and plasma membranes in bloodstream forms of Trypanosoma brucei - Solving the three-compartment problem, European Journal of Biochemistry, 267, (15), 2000, p4601 - 4614 Journal Article, 2000 DOI

Nolan D.P., Geuskens M., and Pays E., N-linked glycans containing linear poly-N-acetyllactosamine as sorting signals in endocytosis in Trypanosoma brucei, Current Biology, 9, 1999, p1169 - 1172 Journal Article, 1999

Pays, E. and Nolan, D.P., Expression and function of surface proteins in Trypanosoma brucei, Mol. Biochem. Parasitol., 91, 1998, p4 - 36 Journal Article, 1998

Rolin, S., Hanocq-Quertier, J., Paturiaux-Hanocq, F., Nolan, D.P. & Pays, E, Mild acid stress as a differentiation trigger in Trypanosoma brucei, Mol. Biochem. Parasitol., 93, 1998, p251 - 262 Journal Article, 1998

Salmon, D., Hanocq-Quertier, J., Paturiaux-Hanocq, F., Pays, A., Tebabi, P., Nolan, D.P., Michel, A. and Pays, E., Characterization of the ligand-binding site of the transferrin receptor in Trypanosoma brucei demonstrates a structural relationship with the N-terminal domain of the variant surface glycoprotein, EMBO J., 16, 1997, p7272 - 7278 Journal Article, 1997

Nolan, D., Jackson, D. G., Windle, H. J., Pays, A., Geuskens, M., Michel, A., Voorheis, H. P. and Pays, E., Characterization of a novel, stage-specific, invariant surface protein in Trypanosoma brucei containing an internal, serine-rich, repetitive motif, Journal of Biological Chemistry, 272, (46), 1997, p29212 - 29221 Journal Article, 1997 DOI

NOLAN, DP, JACKSON, DG, WINDLE, HJ, PAYS, A, GEUSKENS, M, MICHELI, A, VOORHEIS, HP, PAYS, E, CHARACTERIZATION OF A NOVEL, STAGE-SPECIFIC, INVARIANT SURFACE PROTEIN IN TRYPANOSOMA BRUCEI CONTAINING AN INTERNAL, SERINE-RICH, REPETITIVE MOTIF, JOURNAL OF BIOLOGICAL CHEMISTRY, 272, 1997, p29212 - 29221 Journal Article, 1997

Rolin, S., Hanocq-Quertier, J., Paturiaux-Hanocq, F., Nolan, D., Salmon, D., Webb, H., Carrington, M., Voorheis, P. & Pays, E., Simultaneous but independent activation of adenylate cyclase and glycosylphosphatidylinositol-phospholipase C under stress conditions in Trypanosoma brucei, Journal of Biological Chemistry, 271, 1996, p10844 - 10852 Journal Article, 1996 DOI

Rolin, S., Hanocq-Quertier, J., Paturiaux-Hanocq, F., Nolan, D., Salmon., D.,Webb, H., Carrington, M., Voorheis, P. and Pays, E., Simultaneous but independent activation of adenylate cyclase and glycosylphosphatidylinositol specific phospholipase C under stress conditions in Trypanosoma brucei, J. Biol. Chem., 271, 1996, p10844 - 10854 Journal Article, 1996

Salmon, D., Geuskens, M., Hanocq, F., Hanocq-Quertier, J., Nolan, D., Ruben, L. & Pays, E., A novel heterodimeric transferrin receptor encoded by a pair of VSG expression site-Associated genes in T. brucei, Cell, 78, 1994, p75 - 86 Journal Article, 1994

Nolan, D.P., Revelard, P. and Pays, E., The characterization and over expression of a gene for the Ca2+ ATPase of the endoplasmic reticulum of Trypanosoma brucei, J. Biol. Chem., 269, 1994, p26045 - 26051 Journal Article, 1994

Nolan, D.P., Revelard, P., Pays, E., Overexpression and Characterization of a Gene for a Ca2+-ATPase of the Endoplasmic Reticulum in Trypanosoma brucei, Journal of Biological Chemistry, 269, (42), 1994, p26045-26051 Journal Article, 1994

Pays, E., Hanocq-Quertier, J., Hanocq, F., Van Assel, S., Nolan, D. and Rolin,S., Abrupt RNA changes precede the first cell division during the differentiation of Trypanosoma brucei bloodstream forms into procyclic forms in vitro, Mol. Biochem. Parasitol., 61, 1993, p107 - 114 Journal Article, 1993

NOLAN, DP, VOORHEIS, HP, THE MITOCHONDRION IN BLOOD-STREAM FORMS OF TRYPANOSOMA-BRUCEI IS ENERGIZED BY THE ELECTROGENIC PUMPING OF PROTONS CATALYZED BY THE F1F0-ATPASE, EUROPEAN JOURNAL OF BIOCHEMISTRY, 209, 1992, p207 - 216 Journal Article, 1992

Nolan, D. P. & Voorheis, H. P., The mitochondrion in bloodstream forms ofTrypanosoma brucei is energized by the electrogenic pumping of protons catalysed by the F1F0 ATPase, European Journal of Biochemistry , 209, (1), 1992, p207 - 216 Journal Article, 1992 DOI

NOLAN, DP, VOORHEIS, HP, THE DISTRIBUTION OF PERMEANT IONS DEMONSTRATES THE PRESENCE OF AT LEAST 2 DISTINCT ELECTRICAL GRADIENTS IN BLOOD-STREAM FORMS OF TRYPANOSOMA-BRUCEI, EUROPEAN JOURNAL OF BIOCHEMISTRY, 202, 1991, p411 - 420 Journal Article, 1991

Nolan, D. P. & Voorheis, H. P., The distribution of permeant ions demonstrates the presence of at least two distinct electrical gradients in bloodstream forms of Trypanosoma brucei, European Journal of Biochemistry, 202, (2), 1991, p411 - 420 Journal Article, 1991 DOI

NOLAN, DP, VOORHEIS, HP, BIOENERGETICS STUDIES OF BLOOD-STREAM FORMS OF TRYPANOSOMA-BRUCEI - ELECTRICAL AND H+ GRADIENTS, BIOCHEMICAL SOCIETY TRANSACTIONS, 18, 1990, p735 - 739 Journal Article, 1990

Nolan, D. P. & Voorheis, H. P., Bioenergetic Studies of Bloodstream Forms of Trypanosoma brucei: Electrical and H+ Gradients, Biochemical Society Transactions , 18, (5), 1990, p735 - 739 Journal Article, 1990

Cronín, C.N., Nolan, D.P., Paul Voorheis, H., The enzymes of the classical pentose phosphate pathway display differential activities in procyclic and bloodstream forms of Trypanosoma brucei, FEBS Letters, 244, (1), 1989, p26-30 Journal Article, 1989

Cronin, C. N., Nolan, D. P. & Voorheis, H. P., The Enzymes of the Classical Pentose Phosphate Pathway Display Differential Activities in Procyclic and Bloodstream Forms of Trypanosoma brucei, FEBS Letters, 244, (1), 1989, p26 - 30 Journal Article, 1989 DOI

CRONIN, CN, NOLAN, DP, VOORHEIS, HP, THE ENZYMES OF THE CLASSICAL PENTOSE-PHOSPHATE PATHWAY DISPLAY DIFFERENTIAL ACTIVITIES IN PROCYCLIC AND BLOOD-STREAM FORMS OF TRYPANOSOMA-BRUCEI, FEBS LETTERS, 244, 1989, p26 - 30 Journal Article, 1989

FEBS letters, 244, (1989), 26 - 30p, vvvvv, [eds.] Journal, 1989

Transformation of Trypanosoma brucei from its bloodstream form into its procyclic form is accompanied by a change in the ionic conductance of the plasma membrane in, editor(s)Keeling, D. & Benham, C. , Ion Transport, London, U.K., Academic Press,, 1989, pp355 , [Nolan, D.P. and Voorheis, H. P.] Book Chapter, 1989

Non-Peer-Reviewed Publications

Nolan, D.P. and Pays, E., Expression and function surface proteins in Trypanosoma brucei, The trypanosome surface Proceedings of the third Francqui colloquium, Francqui Scientific library De Boeck Brussels, 1999, pp5 - 51 Conference Paper, 1999

Research Expertise

Description

. Expression and function of surface proteins in protozoan parasites. Endocytosis, protein traffic and flagellar pocket function.. Parasite Bioenergetics . regulation and function of actin cytoskeleton. . Molecular and cell biology of the African trypanosome Trypanosoma brucei. . Vesicular traffic and the actin cytoskeleton in T. brucei.

Projects

  • Title
    • Polarity and function of actin in vesicle traffic in African trypanosomes
  • Summary
    • This SFI funded research programme seeks to understand how the polarity of the actin cytoskeleton is maintained and the role of this cytoskeleton in vesicle traffic (endocytosis/exocytosis) in African tryapanosmes. sorting of proteins within the unique region of the flagellar pocket
  • Funding Agency
    • SFI
  • Date From
    • 11/04
  • Date To
    • 1106
  • Title
    • Characterization of glycoproteins from the flagellar pocket and endocytic pathway in African trypanosomes: a new paradigm for protein trafficking in a highly polarized cell.
  • Summary
    • The aim of the project is the identifcation and characterization of proteins from the flagellar pocket and endocytic pathway in African trypanosomes and to investigate the mechanisms for specific sorting and routing of proteins to and fromthe pocket
  • Funding Agency
    • Wellcome Trust
  • Date From
    • 12/01
  • Date To
    • 12/09
  • Title
    • "In silico discovery of novel therapeteutics for African Sleeping Sickness.
  • Summary
    • Health Research Board postdoctoral research fellowship (PD/2009/33). 2010-2013 Duration: 36 months. Role college principle investigator/ sponsor for Dr. A Knox
  • Funding Agency
    • HRB
  • Date From
    • 2010
  • Date To
    • 2013
  • Title
    • Organization of the actin cytoskeleton in African trypansomes.
  • Summary
    • Health Research Board postdoctoral research fellowship (PD/2007/10). 2007-2012 Role college principle investigator/ sponsor for Dr. J Rubotham
  • Funding Agency
    • HRB
  • Date From
    • 2007
  • Date To
    • 2012
  • Title
    • "Energy metabolism of trypansomes: towards a better understanding of mitochondrial metabolism"
  • Summary
    • Ulyesses Research visit award 2008 . Role: principle Investigator.
  • Title
    • Flagellar Attachment in African trypanosomes: investigating spatial and temporal co-ordination of proteins in a cell
  • Summary
    • A major question in cell biology is how are proteins, complexes and organelles, positioned in the right place at the right time? Flagella are morphologically striking organelles in eukaryotes, defined by their function in motility. Flagellar replication and inheritance is a visually dramatic example of spatial and temporal co-ordination which is especially obvious in African trypanosomes, e.g. Trypanosoma brucei. These unicellular eukaryotes cause fatal human sleeping sickness and Nagana in domestic animals and are a significant medical, veterinary and economic burden throughout sub-Saharan Africa. The single flagellum of T. brucei emerges from the posterior end of the cell and uniquely is then attached along the cell body through a specialized domain involving the cytoskeleton and surface membranes called the flagellar attachment zone (FAZ), before extending to an anterior free flagellum. This region consists of a series of junctional complexes that are precisely spaced along the FAZ. These complexes can be viewed as molecular rivets that extend from the cell body through the surface and flagellar membranes and to link into the cytoskeletal structure of the flagellum. Attachment requires coordinated, continuous and precise positioning of these rivets as the new flagellum is growing. Trypanosomes divide by binary fission along an axis defined by the new and existing flagellum. Attachment failure results in fission failure and cell death. Little is known about the molecular mechanisms involved or how the process is coordinated. The place to start is functional characterization of proteins required for attachment. This project will investigate novel families of FAZ specific, precisely position surface proteins that are essential for attachment by combining molecular techniques with recent developments in high resolution microscopy. Understanding the function and positioning of these proteins will provide new insights into flagellar attachment and may have translational benefits through identification of new targets for anti-trypanosomes agents.
  • Funding Agency
    • IRC
  • Date From
    • 1/09/2015
  • Date To
    • 31/08/2019
  • Title
    • Role of actin in vesicle traffic in African trypanosomes"
  • Funding Agency
    • SFI 07/RFP/BICF358 (2007-2010)
  • Date From
    • 2007
  • Date To
    • 2010
  • Title
    • Molecular dialogue between parasite and hosts : the trypanosome model
  • Funding Agency
    • Collaborative PIA award (2005-2010) with Prof. Etienne Pays
  • Date From
    • 2005
  • Date To
    • 2010

Keywords

ACIDIC REPETITIVE PROTEIN; AFRICAN TRYPANOSOMES; BLOOD-STREAM FORMS; CELL-SURFACE; CONCANAVALIN-A; CROSS-LINKING; GPI-ANCHORED PROTEINS; LIPOPHILIC CATION; MEMBRANE-POTENTIAL CHANGES; MITOGENIC STIMULATION; NEURO-BLASTOMA; Parasitology; PH GRADIENTS; PHOSPHATIDYLINOSITOL MEMBRANE ANCHOR; PLASMA-MEMBRANE; PROCYCLIC FORMS; PROTON-MOTIVE FORCE; SACCHAROMYCES-CEREVISIAE; SECONDARY STRUCTURE; STREPTOCOCCUS-LACTIS; TRANSFERRIN RECEPTOR

Recognition

Representations

Reviewer for European Journal of Biochemistry; EMBO Journal; Molecular and Biochemical Parasitology; Parasitology Today; J. Cell Science; Molecular Microbiology 2007-

Grant reviewer for: [1] - The National Science Foundation, Washington, D.C. 20550, U.S.A. [2] - The Wellcome Trust (UK), FNRS (Belgium), BBSRC (UK) grant reviewer ERC

Awards and Honours

EMBO long term Fellowship 1992

Marie Curie Fellowship 1994

Memberships

Member of the Biochemical Society London Treasurer of Irish Area Section of Biochemical Society Member of the British Society for Parasitology 2014