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-
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
Pays E, Nolan DP., Genetic and immunological basis of human African trypanosomiasis., Current opinion in immunology, 72, 2021, p13-20
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
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
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
Terry K. Smith, Frédéric Bringaud, Derek P. Nolan, Luisa M. Figueiredo, Metabolic reprogramming during the Trypanosoma brucei life cycle, F1000Research, 2017, p683-
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
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
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
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
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
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
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
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
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
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
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
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
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-
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.]
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.]
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
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
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
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
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.]
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
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.]
) 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. ]
Black, S.J., N. Murphy and D. Nolan, Innate and acquired control of trypanosomiasis in Cape buffalo, Int. J. Parasitol., 31, 2001, p562 - 565
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
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
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
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
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
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
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
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
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
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
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
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
Pays, E. and Nolan, D.P., Expression and function of surface proteins in Trypanosoma brucei, Mol. Biochem. Parasitol., 91, 1998, p4 - 36
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
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
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
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
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
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
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
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
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
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
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
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
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
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
NOLAN, DP, VOORHEIS, HP, BIOENERGETICS STUDIES OF BLOOD-STREAM FORMS OF TRYPANOSOMA-BRUCEI - ELECTRICAL AND H+ GRADIENTS, BIOCHEMICAL SOCIETY TRANSACTIONS, 18, 1990, p735 - 739
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
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
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
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
FEBS letters, 244, (1989), 26 - 30p, vvvvv, [eds.]
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.]
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
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
Recognition
Representations
Reviewer for European Journal of Biochemistry; EMBO Journal; Molecular and Biochemical Parasitology; Parasitology Today; J. Cell Science; Molecular Microbiology
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
Marie Curie Fellowship
Memberships
Member of the Biochemical Society London Treasurer of Irish Area Section of Biochemical Society Member of the British Society for Parasitology