Centre for Biological Sciences

Lindy Holden-Dye

BSc, MSc, PhD

Primary position:
Director of Enterprise
Other positions:
Chair in Neuroscience, Principal Investigator (Neuropharmacology & physiology)

Background

The University of Southampton

Career history

Professor of Neuroscience. University of Southampton, UK.
Reader. School of Biological Sciences, University of Southampton, UK.
Post-doctoral Research Fellow. Department of Neurophysiology, University of Southampton, UK.

Academic qualifications

PhD Neuropharmacology. University of Southampton, UK.
MSc Biochemical Pharmacology. University of Southampton, UK.
BSc Physiology. University College, Cardiff, UK.

Publications

The University of Southampton's electronic library (e-prints)

Article

Dillon, James, Andrianakis, Ioannis, Mould, Richard, Ient, Ben, Liu, Wei, James, Christopher, O'Connor, Vincent and Holden-Dye, Lindy (2013) Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans. The FASEB Journal, 27, (10), 4266-4278. (doi:10.1096/fj.11-189340). (PMID:23882127).
Hu, Chunxiao, Dillon, James, Kearn, James, Murray, Caitriona, O'Connor, Vincent, Holden-Dye, Lindy and Morgan, Hywel (2013) NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae. PLoS ONE, 8, (5), e64297-[17pp]. (doi:10.1371/journal.pone.0064297). (PMID:23717588).
Perney, Nicolas M., Braddick, Lucy, Jurna, Martin, Garbacik, Erik T., Offerhaus, Herman L., Serpell, Louise C., Blanch, Ewan, Holden-Dye, Lindy, Brocklesby, William S. and Melvin, Tracy (2012) Polyglutamine aggregate structure in vitro and in vivo; new avenues for coherent anti-Stokes Raman scattering microscopy. PLoS ONE, 7, (7), e40536. (doi:10.1371/journal.pone.0040536).
Ient, Ben, Edwards, Richard, Mould, Richard, Hannah, Matthew, Holden-Dye, Lindy and O'Connor, Vincent (2012) HSP-4 endoplasmic reticulum (ER) stress pathway is not activated in a C. elegans model of ethanol intoxication and withdrawal. Invertebrate Neuroscience (doi:10.1007/s10158-012-0136-7). (PMID:22661239).
Welz, C., Kruger, N., Schnederjans, M., Miltsch, S.M., Krucken, J., Guest, Marcus, Holden-Dye, L., Harder , A. and von Samson-Himmelstjerna, G. (2011) SLO-1-channels of parasitic nematodes reconstitute locomotor behaviour and emodepside sensitivity in Caenorhabditis elegans slo-1 loss of function mutants. PLoS Pathogens, 7, (4), e1001330. (doi:10.1371/journal.ppat.1001330).
Crisford, Anna, Murray, Caitriona, O'Connor, Vincent, Edwards, Richard J., Kruger, Nina, Welz, Claudia, von Samson-Himmelstjerna, Georg, Harder, Achim, Walker, Robert J. and Holden-Dye, Lindy (2011) Selective toxicity of the anthelmintic emodepside revealed by heterologous expression of human KCNMA1 in caenorhabditis elegans. Molecular Pharmacology, 79, (6), 1031-1043. (doi:10.1124/mol.111.071043). (PMID:21415309 ).
Packham, Rachel, Walker, Robert J. and Holden-Dye, Lindy (2010) The effect of a selective octopamine antagonist, epinastine, on pharyngeal pumping in Caenorhabditis elegans. Invertebrate Neuroscience, 10, (1), 47-52. (doi:10.1007/s10158-010-0107-9). (PMID:20967561).
Lou, Chenguang, Xiao, Qiang, Brennan, Lavinia, Light, Mark E., Vergara-Irigaray, Nuria, Atkinson, Elizabeth M., Holden-Dye, Lindy M.., Fox, Keith R. and Brown, Tom (2010) Synthesis and properties of triplex-forming oligonucleotides containing 2′-O-(2-methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine. Bioorganic & Medicinal Chemistry, 18, (17), 6389-6397. (doi:10.1016/j.bmc.2010.07.005). (PMID:20674370).
Mitchell, Philippa, Mould, Richard, Dillon, James, Glautier, Steven, Andrianakis, Ioannis, James, Christopher, Pugh, Amanda, Holden-Dye, Lindy and O'Connor, Vincent, Hart, Anne C. (ed.) (2010) A differential role for neuropeptides in acute and chronic adaptive responses to alcohol: behavioural and genetic analysis in caenorhabditis elegans. PLoS ONE, 5, (5), e10422. (doi:10.1371/journal.pone.0010422).
Walker, R.J., Papaioannou, S. and Holden-Dye, Lindy (2010) A review of FMRFamide- and RFamide-like peptides in metazoa. Invertebrate Neuroscience (doi:10.1007/s10158-010-0097-7).
Franks, Christopher J., Murray, Caitriona, Ogden, David, O'Connor, Vincent and Holden-Dye, Lindy (2009) A comparison of electrically evoked and channel rhodopsin-evoked postsynaptic potentials in the pharyngeal system of Caenorhabditis elegans. Invertebrate Neuroscience, 9, (1), 43. (doi:10.1007/s10158-009-0088-8).
Graham, Margaret E., Edwards, Mark R., Holden-Dye, Lindy, Morgan, Alan, Burgoyne, Robert D. and Barclay, Jeff W. (2009) UNC-18 modulates ethanol sensitivity in caenorhabditis elegans. Molecular Biology of the Cell, 20, (1), 43-55. (doi:10.1091/mbc.E08-07-0689).
Dillon, James, Andrianakis, Ioannis, Bull, Kate, Glautier, Steve, O'Connor, Vincent, Holden-Dye, L. and James, C.J. (2009) AutoEPG: software for the analysis of electrical activity in the microcircuit underpinning feeding behaviour of caenorhabditis elegans. PLoS ONE , 4, (12), 1-13. (doi:10.1371/journal.pone.0008482).
Bush, Elizabeth, Foreman, Richard, Walker, Robert J. and Holden-Dye, Lindy (2009) The actions of chloride channel blockers, barbiturates and a benzodiazepine on Caenorhabditis elegans glutamate- and ivermectin-gated chloride channel subunits expressed in Xenopus oocytes. Invertebrate Neuroscience, 9, (3-4), 175-184. (doi:10.1007/s10158-010-0096-8). (PMID:20224918).
Walker, R.J., Holden-Dye, Lindy and Papaioannou, Sylvana (2008) The actions of Caenorhabditis elegans neuropeptide-like peptides (Nlps) on body wall muscle of Ascaris suum and pharyngeal muscle of C. elegans. Acta Biologica Hungarica, 59, supplement 2, 189-197. (doi:10.1556/ABiol.59.2008.Suppl.28). (PMID:18652392).
Mitchell, P.H., Bull, K., Glautier, S., Hopper, N.A., Holden-Dye, L. and O'Connor, V. (2007) The concentration-dependent effects of ethanol on Caenorhabditis elegans behaviour. The Pharmacogenomics Journal, 7, (6), 411-417. (doi:10.1038/sj.tpj.6500440).
Guest, Marcus, Bull, Kathryn, Walker, Robert J., Amliwala, Kiran, Connor, Vincent, Harder, Achim, Holden-Dye, Lindy and Hopper, Neil A. (2007) The calcium-activated potassium channel, SLO-1, is required for the action of the novel cyclo-octadepsipeptide anthelmintic, emodepside, in Caenorhabditis elegans. International Journal for Parasitology, 37, (14), 1577-1588. (doi:10.1016/j.ijpara.2007.05.006).
Holden-Dye, Lindy, O’Connor, Vincent, Hopper, Neil A., Walker, Robert J., Harder, Achim, Bull, Kathryn and Guest, Marcus (2007) SLO, SLO, quick, quick, slow: calcium-activated potassium channels as regulators of Caenorhabditis elegans behaviour and targets for anthelmintics. Invertebrate Neuroscience, 7, (4), 199-208. (doi:10.1007/s10158-007-0057-z). (PMID:17962986).
Bull, Kathryn, Cook, Alan, Hopper, Neil A., Harder, Achim, Holden-Dye, Lindy and Walker, Robert J. (2006) Effects of the novel anthelmintic emodepside on the locomotion, egg-laying behaviour and development of Caenorhabditis elegans. International Journal for Parasitology (doi:10.1016/j.ijpara.2006.10.013).
Dillon, J., Hopper, N.A., Holden-Dye, L. and Connor, V. (2006) Molecular characterization of the metabotropic glutamate receptor family in Caenorhabditis elegans. Biochemical Society Transactions, 34, (5), 942-948.
Franks, Christopher J., Holden-Dye, Lindy, Bull, Kathryn, Luedtke, Sarah and Walker, Robert J. (2006) Anatomy, physiology and pharmacology of Caenorhabditis elegans pharynx: a model to define gene function in a simple neural system. Invertebrate Neuroscience, 6, (3), 105-122. (doi:10.1007/s10158-006-0023-1). (PMID:16862440).
Holden-Dye, Linda and Walker, Robert J. (2006) Actions of glutamate and ivermectin on the pharyngeal muscle of Ascaridia galli: A comparative study with Caenorhabditis elegans. International Journal for Parasitology, 36, (4), 395-402. (doi:10.1016/j.ijpara.2005.11.006 ).
Cook, Alan, Aptel, Nathalie, Portillo, Virginia, Siney, Elodie, Sihota, Rajinder, Holden-Dye, Lindy and Wolstenholme, Adrian (2006) Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors. Molecular and Biochemical Parasitology, 147, (1), 118-125. ( doi:10.1016/j.molbiopara.2006.02.003).
Vinogradova, Irina, Cook, Alan and Holden-Dye, Lindy (2006) The ionic dependence of voltage-activated inward currents in the pharyngeal muscle of Caenorhabditis elegans. Invertebrate Neuroscience, 6, (2), 57-68. (doi:10.1007/s10158-006-0018-y).
Papaioannou, Sylvana, Marsden, David, Franks, Christopher J., Walker, Robert J. and Holden-Dye, Lindy (2005) Role of a FMRFamide-like family of neuropeptides in the pharyngeal nervous system of Caenorhabditis elegans. Journal of Neurobiology, 65, (3), 304-319. (doi:10.1002/neu.20201).
Spanier, B., Sturzenbaum, S.R., Holden-Dye, L.M. and Baumeister, R. (2005) Caenorhabditis elegans Neprilysin nep-1: An effector of locomotion and pharyngeal pumping. Journal of Molecular Biology, 352, (2), 429-437. (doi:10.1016/j.jmb.2005.06.063).
Amliwala, K., Bull, K., Willson, J., Harder, A., Holden-Dye, L. and Walker, R.J. (2004) Emodepside, a cyclo-octadepsipeptide anthelmintic with a novel mode of action. Drugs of the Future, 29, (10), 1015-1024. (doi:10.1358/dof.2004.029.10.863392).
Willson, J., Amliwala, K., Davis, A., Cook, A., Cuttle, M.F., Kriek, N., Hopper, N.A., O'Connor, V., Harder, A., Walker, R.J. and Holden-Dye, L. (2004) Latrotoxin receptor signaling engages the UNC-13-dependent vesicle-priming pathway in C. elegans. Current Biology, 14, (15), 1374-1379. (doi:10.1016/j.cub.2004.07.056).
Willson, J., Amliwala, K., Davis, A., Cook, A., Cuttle, M.F., Kriek, N., Hopper, N.A., Connor, V., Harder, A., Walker, R.J. and Holden-Dye, L. (2004) Latrotoxin receptor signaling engages the UNC-13-dependent vesicle-priming pathway in C. elegans. Current Biology, 14, (24), 1374-1379. (doi:10.1016/j.cub.2004.12.036).
Holden-Dye, Lindy, Walker, R.J. and Franks, C.J. (2004) A Structure-Activity study of the neuropeptide PF1, SDPNFLRFamide, using the dorsal body wall muscle of the chicken nematode, Ascaridia galli. Acta Biologica Hungarica, 55, (1), 343-351. (doi:10.1556/ABiol.55.2004.1-4.40). (PMID:15270251).
Keating, C.D., Kriek, N, Daniels, M, Ashcroft, N.R., Hopper, N.A., Siney, E.J., Holden-Dye, L and Burke, J.F. (2003) Whole-genome analysis of 60 G protein-coupled receptors in Caenorhabditis elegans by gene knockout with RNAi. Current Biology, 13, (19), 1715-1720. (doi:10.1016/j.cub.2003.09.003).
Keating, C.D., Kriek, N., Daniels, M., Ashcroft, N.R., Hopper, N.A., Siney, E.J., Holden-Dye, L. and Burke, J.F. (2003) Whole-genome analysis of 60 G protein-coupled receptors in Caenorhabditis elegans by gene knockout with RNAi. Current Biology, 13, (19), 1715-1720. (doi:10.1016/j.cub.2003.09.003).
Harder, A., Schmitt-Wrede, H.P., Krucken, J., Marinovski, P., Wunderlich, F., Willson, J., Amliwala, K., Holden-Dye, L. and Walker, R. (2003) Cyclooctadepsipeptides - an anthelmintically active class of compounds exhibiting a novel mode of action. International Journal of Antimicrobial Agents, 22, (3), 318-331. (doi:10.1016/S0924-8579(03)00219-X).
Willson, J., Amliwala, K., Harder, A., Holden-Dye, L. and Walker, R.J. (2003) The effect of the anthelmintic emodepside at the neuromuscular junction of the parasitic nematode Ascaris suum. Parasitology, 126, (1), 79-86. (doi:10.1017/S0031182002002639).
Holden-Dye, Lindy and Walker, Robert J. (2002) Synaptic modulation of the pharyngeal muscle of C. elegans. Journal of Physiology, 543P, (S324), p.4S.
Amliwala, K., Willson, J., Holden-Dye, L., Harder, A. and Walker, R.J. (2002) Effect of the anthelmintic emodepside on locomotion in C-elegans, and on the somatic muscle of A-suum. Journal of Physiology, 543, (S222), 1P-2P.
Papaioannou, S., Holden-Dye, L. and Walker, R.J. (2002) Physiological actions of putative neuropeptides in the nematode Ascaris suum. Journal of Physiology, 543, (225), 3P-4P.
Franks, Christopher J., Pemberton, Darrel, Vinogradova, Irina, Cook, Alan, Walker, Robert J. and Holden-Dye, Lindy (2002) Ionic basis of the resting membrane potential and action potential in the pharyngeal muscle of Caenorhabditis elegans. Journal of Neurophysiology, 87, (2), 954-961.
Willson, J., Holden-Dye, L., Harder, A. and Walker, R.J. (2001) A possible mechanism for the action of the novel anthelmintic emodepside, using Ascaris suum body wall muscle preparations. Journal of Physiology, 536P, (S103), 132P-133P.
Rogers, Candida M., Franks, Christopher J., Walker, Robert J., Burke, Julian F. and Holden-Dye, Lindy (2001) Regulation of the pharynx of Caenorhabditis elegans by 5-HT, octopamine, and FMRFamide-like neuropeptides. Journal of Neurobiology, 49, (3), 235-244. (doi:10.1002/neu.1078).
Trim, J.E., Holden-Dye, L., Willson, J., Lockyer, M. and Walker, R.J. (2001) Characterization of 5-HT receptors in the parasitic nematode, Ascaris suum. Parasitology, 122, (2), 207-217. (doi:10.1017/S003118200100703X).
Pemberton, Darrel J., Franks, Christopher J., Walker, Robert J. and Holden-Dye, Lindy (2001) Characterization of glutamate-gated chloride channels in the pharynx of wild-type and mutant Caenorhabditis elegans delineates the role of the subunit GluCl-α2 in the function of the native receptor. Molecular Pharmacology, 59, (5), 1037-1043.
Gieseler, K., Mariol, M.C., Bessou, C., Migaud, M., Franks, C.J., Holden-Dye, L. and Segalat, L. (2001) Molecular, genetic and physiological characterisation of dystrobrevin-like (dyb-1) mutants of Caenorhabditis elegans. Journal of Molecular Biology, 307, (1), 107-117. (doi:10.1006/jmbi.2000.4480).
Bascal, Z.A., Cunningham, J.M., Holden-Dye, L., Shea, M. and Walker, R.J. (2001) Characterization of a putative nitric oxide synthase in the neuromuscular system of the parasitic nematode, Ascaris suum. Parasitology, 122, (2), 219-232. (doi:10.1017/S003118200100720X ).
Walker, R.J., Franks, C.J., Pemberton, D., Rogers, C. and Holden-Dye, L. (2000) Physiological and pharmacological studies on nematodes. Acta Biologica Hungarica, 51, (2-4), 379-394.
Brownlee, David, Holden-Dye, Lindy and Walker, Robert (2000) The range and biological activity of FMRFamide-related peptides and classical neurotransmitters in nematodes. Advances in Parasitology, 45, 109-180. (doi:10.1016/S0065-308X(00)45004-9).
Garland, C.M., Foreman, R.C., Chad, J.E., Holden-Dye, L. and Walker, R.J. (1998) The actions of muscle relaxants at nicotinic acetylcholine receptor isoforms. European Journal of Pharmacology, 357, (1), 83-92. (doi:10.1016/S0014-2999(98)00542-1).

Book Section

Harder, A., Bull, K., Guest, Marcus, Holden-Dye, Lindy and Walker, R.J. (2009) Cyclo-octadepsipeptides – an anthelmintically active class of compounds exhibiting a novel mode of action. In, Selzer, P.M. (ed.) Antiparasitic and Antibacterial Drug Discovery: From Molecular Targets to Drug Candidates. , Wiley-VCH, 339-356.
Holden-Dye, L. and Walker, Robert J. (2007) Anthelmintic drugs. In, Maricq, V. (ed.) WormBook: The Online Review of C. elegans Biology. , The C. elegans Research Community. (doi:10.1895/wormbook.1.143.1).
Willson, J., Walker, R.J., Holden-Dye, Lindy and Harder, A. (2004) The action of cyclo-octadepsipeptide anthelmintics on the free-living nematode, Caenorhabditis elegans. In, Beadle, D.J., Mellor, I.R. and Usherwood, P.N.R. (eds.) Neurotoxicological Targets from Functional Genomics and Proteomics, Society of the Chemical Industry Neurotox’03. Neurotox'03 , Society of Chemical Industry, 123-130.
Walker, R.J., Rogers, C.M., Franks, C.J. and Holden-Dye, Lindy (2004) Electrophysiological and pharmacological studies on excitable tissues in nematodes. In, Cell Signalling in Prokaryotes and Lower Metazoa. , Springer, 243-301.

Conference or Workshop Item

Crisford, Anna, Marvin, Jessica, Ludlow, Elisabeth, Lilley, Catherine, O’Connor, Vincent, Urwin, Peter and Holden-Dye, Lindy (2014) Characterising nicotinic acetylcholine receptors in the plant parasitic nematode Globodera pallida. In, Nicotinic Acetylcholine Receptors 2014, Cambridge, GB, 23 - 26 Jul 2014. 1pp.
Hu, Chunxiao, O'Connor, Vincent, Holden-Dye, L. and Morgan, Hywel (2012) An integrated microfluidic device for high-throughput electrophysiological analysis of c. elegans. In, Proceedings of 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences , Okinawa, JP, 28 Oct - 01 Nov 2012.

Additional publications

Holden-Dye L and Walker RJ. Anthelmintic Drugs. (2007) WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook. http://www.wormbook.org.

Franks CJ, Holden-Dye L, Bull K, Luedtke S, Walker RJ. (2006) Anatomy, physiology and pharmacology of Caenorhabditis elegans pharynx: a model to define gene function in a simple neural system. Invert Neurosci. 6:105-22

 

Research

Research Interests

I am interested in the fundamental processes of neuronal communication and have established research expertise in simple invertebrate preparations. Much of my work now resonates with issues concerning mental health such as addiction and neurodegeneration. My expertise in invertebrate neuroscience, and in particular nematode neural systems and C. elegans, positions me well to participate in drug discovery and mode of action programmes for novel antiparasitics. For the last decade I have collaborated with industry to improve prospects for parasitic nematode control. The experimental approaches deployed in my research encompass genetics through to whole animal physiology and incorporate novel methods for tracking animal behaviour and signal processing.

Primary research group:  Biomedical Sciences

Affiliate research groups:  Institute for Life Sciences (IfLS), Southampton Neuroscience Group (SoNG)

Research projects

Are GTGs a new class of plant anion channels regulating pH in the endomembrane system?

Given the significant sequence similarity between members of the GTG/GPHR family, we are testing whether the GTG/GPHR family has a conserved physiological function in diverse organisms.

Characterisation of cue-dependent behaviour in plant parasitic nematodes: the neurobiology of host plant invasion

The neurobiology of plant parasitic nematodes.

Exploiting C. elegans to provide insight into neural substrates of human alcohol dependence

Changes in the pattern of behavior with increasing alcohol intake in humans reflect its complex effects on the brain.

Teaching Responsibilities

Module coordinator

BIOL1011 Foundations of Physiology I 
BIOL1013 Cell Communications Foundations of Physiology
BIOL2016 Pharmacology A
BIOL2014 Neuroscience 
BIOL2017 Pharmacology B
BIOL3021 Cellular and Molecular Neuroscience 
BIOL3027 Selective toxicity 
BIOL3018 Molecular Pharmacology 
BIOL3020 Systems Neuroscience 
BIOL3025 Neuropharmacology of CNS Disorders

Contributions to postgraduate teaching programme

BIOL3050 Short Research Project
BIOL3034 In-depth Research Project
BIOL3031 Literature-based Research Project
BIOL3032 Literature-based Research Project
BIOL2016 Pharmacology A
BIOL2014 Neuroscience

Other teaching related responsibilities

Neuroscience tutorials for second year
Contribution to two modules at Winchester School of Art, one in fashion design and the other in graphic arts by providing briefs for neuroscience inspired projects (2 launches in this academic year).
Contribution to Faculty of Medicine, Scientific Basis of Medicine module (Alcohol)

Contact

Professor Lindy Holden-Dye
FNES Student Office
Centre for Biological Sciences
Faculty of Natural & Environmental Sciences
Life Sciences Building 85
University of Southampton
Highfield Campus
Southampton
SO17 1BJ

Room Number: 85/3051