Dr Richard Billington
Profiles

Dr Richard Billington

Associate Professor of Biology

School of Biological and Marine Sciences (Faculty of Science and Engineering)

Dr Richard Billington can be contacted through arrangement with our Press Office, to speak to the media on these areas of expertise.
  • Biochemistry
  • Pharmacology
  • Inverterbrate biology
  • Dragonflies
  • Birds
  • Cancer biology
Biography

Biography

Radiation Protection Supervisor
Associate Head of School (Biology Subject Group Lead)

My background is in Biochemistry and Biochemical Pharmacology and I am particularly interested in signalling pathways that involve pyridine nucleotides. My interests also extend to many other areas as Biochemical techniques can be used to study a huge array of processes.

I am also a Biologist with particular interests in birds, mammals (terrestrial and marine), reptiles, medicinal plants, and a number of invertebrate groups including Odonata, Isopods, Shieldbugs, Bees, Butterflies and whatever else happens to be a nice small group with a good ID book/key that not many people are interested in. I am currently interested in linking invertebrate biochemistry to ecological studies and using lab-based techniques to compliment ecological studies.

Qualifications

Degree:
1996-1999 Biochemistry, University of Bristol
PhD: 
1999-2002 Department of Pharmacology, University of Cambridge
Postdoc:
2002-2003 Department of Pharmacology, University of Cambridge (Biotechnology and Biological Sciences Research Council) 2003-2005 Università degli Studi del Piemonte Orientale. 
Teaching

2006-2008 “Ricercatore” at the Università degli Studi del Piemonte Orientale, Novara, Italy.

Professional membership

FLS

Teaching

Teaching

Teaching interests

I teach on a wide variety of modules from biochemistry, cell biology and pharmacology right up to field biology.

As a naturalist at heart, I attend a number of field courses both in the UK and abroad.

Research

Research

Research interests

Pyridine nucleotides and their roles in basic metabolism and signalling

NAD(P) has long been thought of as a simple redox co-factor involved in basic metabolism but recent findings show that it is also involved in cell signalling pathways. These pathways include fundamental processes such as gene expression (via the Sirtuin enzymes), DNA repair (via PARP; poly ADP-ribose polymerase), posttranslational protein modification (via PARP and ADP-ribosyl tranferases; ART) and Ca2+-signalling (via CD38 metabolites). Furthermore, it has been shown that the maintenance of high intracellular NAD levels can prolong the lifespan of cells probably in a Sirtuin-dependent manner. Many of these roles have been elucidated only recently and we are still only beginning to understand the wide-ranging implications that pyridine nucleotide signalling may have in the cell. My research is aimed at elucidating some of the fundamental processes which control and are controlled by pyridine nucleotides and their derivatives.

Pyridine nucleotide homeostasis as a pharmacological target

The widespread involvement of NAD(P) in signalling pathways has also led to the hypothesis that such NAD(P)-mediated processes and NAD(P) homeostasis pathways could be promising drug targets for a wide range of diseases, in particular cancer and diabetes but also neurodegeneration, obesity and psoriasis to name a few. Although we are still some way off the clinical use of such drugs, my research aims to highlight novel targets and mechanisms that could provide therapeutics in the future.

Ca2+-signalling with particular respect to pyridine nucleotide second messengers.

The enzyme CD38 is a multifunctional cell surface enzyme and receptor. Two of its enzymatic products, cADPR and NAADP (metabolites of NAD and NADP), have been shown to be potent releasers of intracellular Ca2+ via the Ryanodine receptor and Two Pore Channels (TPC) respectively. Little is know still about the mechanisms that control the actions of these two messengers and my research is aimed at elucidating these mechanisms.

The generation of specificity/complexity and its decoding in signalling pathways.

Cell signalling pathways must specifically control only selected target proteins. Indeed, many disease states are caused by the inappropriate or dysregulated activation of non target proteins. In order to acheive this, cellular signals must necessarily include a certain level of complexity (for instance variation of the spatial and temporal parameters). There is still much to understand about how levels of complexity are both encoded and decoded such that only specific targets respond.

Immune function in invertebrates

Invertebrates lack an adaptive immune system such as that found in mammals and must rely on their innate mechanisms for combatting pathogens and parasites. I am interested in the biochemistry of the mechanisms applied by invertebrates to achieve this and linking immune function to ecology and rarity.

Invasive species

Invasives have always been fascinating to me and I am interested in the spread and survival of such species, mostly with terrestrial invertebrates. My definition of invasive is lax and I also include colonising species
Publications

Publications

Key publications

Key publications are highlighted

Journals
Articles
Huml JV, Ellis JS, Rustage S, Brown MJF, Billington R & Knight ME (2023) 'The tragedy of the common? A comparative population genomic study of two bumblebee species' Insect Conservation and Diversity , DOI Open access
Botella-Cruz M, Pallares S, Velasco J, Moody AJ, Billington R, Millan A & Bilton D (2022) 'The colonization of saline waters is associated with lowered immune responses in aquatic beetles' Freshwater Biology , DOI Open access
Hesketh-Best PJ, Mouritzen MV, Shandley-Edwards K, Billington RA & Upton M (2021) 'Galleria mellonella larvae exhibit a weight-dependent lethal median dose when infected with methicillin-resistant Staphylococcus aureus' Pathogens and Disease 79, (2) , DOI Open access
Mansur AA, Brown MT & Billington RA (2020) 'The cytotoxic activity of extracts of the brown alga Cystoseira tamariscifolia (Hudson) Papenfuss, against cancer cell lines changes seasonally' Journal of Applied Phycology , DOI Open access
Hanley M, sanders S, Stanton H-M, Billington R & Boden R (2019) 'A pinch of salt: response of coastal grassland plants to simulated seawater inundation treatments' Annals of Botany , DOI Open access
Cioffi R, Moody AJ, Millán A, Billington RA & Bilton DT (2016) 'Physiological niche and geographical range in European diving beetles (Coleoptera: Dytiscidae)' Biology letters 12, (6) , DOI Open access
Al-Shabany AJ, Moody AJ, Foey AD & Billington RA (2016) 'Intracellular NAD+ levels are associated with LPS-induced TNF-α release in pro-inflammatory macrophages' Bioscience Reports 36, (1) 0-0 , DOI Open access
Almzaiel AJ, Billington R, Smerdon G & Moody AJ (2015) 'Hyperbaric oxygen enhances neutrophil apoptosis and their clearance by monocyte-derived macrophages' Biochemistry and Cell Biology 93, (4) 405-416 , DOI
Al-Abady ZN, Durante B, Moody AJ & Billington RA (2013) 'Large changes in NAD levels associated with CD38 expression during HL-60 cell differentiation' Biochem Biophys Res Commun 442, (1-2) 51-55 Author Site , DOI
Almzaiel AJ, Billington R, Smerdon G & Moody AJ (2013) 'Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells' Life Sci 93, (2-3) 125-131 Author Site , DOI
Hawar S, Vevers W, Karieb S, Ali BK, Billington R & Beal J (2013) 'Biotransformation of patulin to hydroascladiol by <i>Lactobacillus plantarum</i>' FOOD CONTROL 34, (2) 502-508 , DOI
Al-Abady? ZN, Ferguson NS, John Moody A & Billington RA (2012) 'CD38 expression regulates NAD(H) levels in human leukemia cells' Free Radical Biology and Medicine 53, S122-S123 , DOI
Conforti L, Wilbrey A, Morreale G, Janeckova L, Beirowski B, Adalbert R, Mazzola F, Di Stefano M, Hartley R & Babetto E (2009) 'Wld S protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice' J Cell Biol 184, (4) 491-500 Author Site , DOI
Gambara G, Billington RA, Debidda M, D'Alessio A, Palombi F, Ziparo E, Genazzani AA & Filippini A (2008) 'NAADP-induced Ca(2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae' J Cell Physiol 216, (2) 396-404 Author Site , DOI
Tron GC, Pirali T, Billington RA, Canonico PL, Sorba G & Genazzani AA (2008) 'ChemInform Abstract: Click Chemistry Reactions in Medicinal Chemistry: Applications of the 1,3‐Dipolar Cycloaddition Between Azides and Alkynes' ChemInform 39, (24) , DOI
Galli U, Ercolano E, Carraro L, Blasi Roman CR, Sorba G, Canonico PL, Genazzani AA, Tron GC & Billington RA (2008) 'Synthesis and biological evaluation of isosteric analogues of FK866, an inhibitor of NAD salvage' ChemMedChem 3, (5) 771-779 Author Site , DOI
Billington RA, Genazzani AA, Travelli C & Condorelli F (2008) 'NAD depletion by FK866 induces autophagy' Autophagy 4, (3) 385-387 Author Site , DOI
Billington RA, Travelli C, Ercolano E, Galli U, Roman CB, Grolla AA, Canonico PL, Condorelli F & Genazzani AA (2008) 'Characterization of NAD uptake in mammalian cells' J Biol Chem 283, (10) 6367-6374 Author Site , DOI
Tron GC, Pirali T, Billington RA, Canonico PL, Sorba G & Genazzani AA (2008) 'Click chemistry reactions in medicinal chemistry: applications of the 1,3-dipolar cycloaddition between azides and alkynes' Med Res Rev 28, (2) 278-308 Author Site , DOI
Genazzani AA & Billington RA (2008) '[Pharmacokinetic and pharmacodynamic features of palonosetron]' Tumori 94, (2) Author Site
Billington RA & Genazzani AA (2007) 'PPADS is a reversible competitive antagonist of the NAADP receptor' Cell Calcium 41, (6) 505-511 Author Site , DOI
Pirali T, Gatti S, Di Brisco R, Tacchi S, Zaninetti R, Brunelli E, Massarotti A, Sorba G, Canonico PL & Moro L (2007) 'Estrogenic analogues synthesized by click chemistry' ChemMedChem 2, (4) 437-440 Author Site , DOI
Deaglio S, Vaisitti T, Billington R, Bergui L, Omede P, Genazzani AA & Malavasi F (2007) 'CD38/CD19: a lipid raft-dependent signaling complex in human B cells' BLOOD 109, (12) 5390-5398 , DOI
Billington RA, Harper C, Bellomo EA, Publicover S, Barratt CLR & Genazzani AA (2006) 'Characterization of cyclic adenine dinucleotide phosphate ribose levels in human spermatozoa' Fertil Steril 86, (4) 891-898 Author Site , DOI
Billington RA, Bellomo EA, Floriddia EM, Erriquez J, Distasi C & Genazzani AA (2006) 'A transport mechanism for NAADP in a rat basophilic cell line' FASEB J 20, (3) 521-523 Author Site , DOI
Moccia F, Billington RA & Santella L (2006) 'Pharmacological characterization of NAADP-induced Ca<SUP>2+</SUP> signals in starfish oocytes' BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 348, (2) 329-336 , DOI
Billington RA, Bruzzone S, De Flora A, Genazzani AA, Koch-Nolte F, Ziegler M & Zocchi E (2006) 'Emerging functions of extracellular pyridine nucleotides' Mol Med 12, (11-12) 324-327 Author Site , DOI
Floriddia EM, Pace D, Genazzani AA, Canonico PL, Condorelli F & Billington RA (2005) 'Sphingosine releases Ca2+ from intracellular stores via the ryanodine receptor in sea urchin egg homogenates' Biochem Biophys Res Commun 338, (3) 1316-1321 Author Site , DOI
Appendino G, Prosperini S, Valdivia C, Ballero M, Colombano G, Billington RA, Genazzani AA & Sterner O (2005) 'SERCA-inhibiting activity of C-19 terpenolides from Thapsia garganica and their possible biogenesis' J Nat Prod 68, (8) 1213-1217 Author Site , DOI
Billington RA, Tron GC, Reichenbach S, Sorba G & Genazzani AA (2005) 'Role of the nicotinic acid group in NAADP receptor selectivity' Cell Calcium 37, (1) 81-86 Author Site , DOI
Billington RA, Bak J, Martinez-Coscolla A, Debidda M & Genazzani AA (2004) 'Triazine dyes are agonists of the NAADP receptor' Br J Pharmacol 142, (8) 1241-1246 Author Site , DOI
Billington RA, Thuring JW, Conway SJ, Packman L, Holmes AB & Genazzani AA (2004) 'Production and characterization of reduced NAADP (nicotinic acid-adenine dinucleotide phosphate)' Biochem J 378, (Pt 1) 275-280 Author Site , DOI
Billington RA, Ho A & Genazzani AA (2002) 'Nicotinic acid adenine dinucleotide phosphate (NAADP) is present at micromolar concentrations in sea urchin spermatozoa' J Physiol 544, (Pt 1) 107-112 Author Site , DOI
Bak J, Billington RA & Genazzani AA (2002) 'Effect of luminal and extravesicular Ca2+ on NAADP binding and release properties' Biochem Biophys Res Commun 295, (4) 806-811 Author Site , DOI
Genazzani AA & Billington RA (2002) 'NAADP: an atypical Ca2+-release messenger?' Trends Pharmacol Sci 23, (4) 165-167 Author Site , DOI
Bak J, Billington RA, Timar G, Dutton AC & Genazzani AA (2001) 'NAADP receptors are present and functional in the heart' Curr Biol 11, (12) 987-990 Author Site , DOI
Billington RA & Genazzani AA (2000) 'Characterization of NAADP(+) binding in sea urchin eggs' Biochem Biophys Res Commun 276, (1) 112-116 Author Site , DOI
Reviews
Plattner H, Sehring IM, Mohamed IK, Miranda K, De Souza W, Billington RA, Genazzani AA & Ladenburger E-M (2012) 'Calcium signaling in closely related protozoan groups (Alveolata): Non-parasitic ciliates (Paramecium, Tetrahymena) vs. parasitic Apicomplexa (Plasmodium, Toxoplasma)' Cell Calcium 51, 351-382
Books
(2005) Calcium Signaling. CRC Press , DOI
Chapters
Morgan AJ, Churchill GC, Masgrau R, Ruas M, Davis LC, Billington RA, Patel S, Yamasaki M, Thomas JM & Genazzani AA (2006) 'Methods in Cyclic ADP-Ribose and NAADP Research' in Putney JW Calcium signaling CRC Press 265-334
Conference Papers
Al-Shabany A, Moody AJ, Foey AD & Billington RA (2014) 'Pharmacological modulation of NAD alters TNF-α responses in macrophage subsets' 180-180 Open access
Al-Shabany A, Moody J, Foey AD & Billington RA (2013) 'NAD levels modulate macrophage subset responses' 92-92
Erriquez J, Bernascone S, Billington R, Grilli MG, Genazzani AA & Distasi C (2006) 'Calcium signals induced by extracellular application of NAADP in developing neurons and glial cells' S10-S11
Billington RA, Bruzzone S, De Flora A, Genazzani AA, Koch-Nolte F, Ziegler M & Zocchi E (2006) 'Emerging functions of extracellular pyridine nucleotides' 324-327 , DOI