Dr Richard Billington
Lecturer in Biochemistry
School of Biological Sciences (Faculty of Science & Environment)
Programme leader BSc Biological Sciences
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.
1996-1999 Biochemistry, University of Bristol
1999-2002 Department of Pharmacology, University of Cambridge
2002-2003 Department of Pharmacology, University of Cambridge (Biotechnology and Biological Sciences Research Council) 2003-2005 Università degli Studi del Piemonte Orientale.
2006-2008 “Ricercatore” at the Università degli Studi del Piemonte Orientale, Novara, Italy.
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.
Invasives have always been fascinating to me and I am interested in spread and survival of such species, mostly with terrestrial invertebrates. My definition of invasive is lax and I also include colonising species
Al-Abady ZN, Durante B, Moody AJ, Billington RA. Large changes in NAD levels associated with CD38 expression during HL-60 cell differentiation. Biochem Biophys Res Commun. (2013) 442(1-2):51-5
Almzaiel AJ, Billington R, Smerdon G, Moody AJ. Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells. Life Sci. (2013) 93(2-3):125-31
Hawar S, Vevers W, Karieb S, Ali BK, Billington R, Beal J. Biotransformation of patulin to hydroascladiol by Lactobacillus plantarum. Food Control (2013) 34(2): 502-508.
Plattner H, Sehring IM, Mohamed IK, Miranda K, De Souza W, Billington RA, Genazzani A, Ladenburger EM. Calcium signaling in closely related protozoan groups (Alveolata): Non-parasitic ciliates (Paramecium, Tetrahymena) vs. parasitic Apicomplexa (Plasmodium, Toxoplasma). Cell Calcium.(2012) 51(5):351-82.
Gambara G, Billington RA, Debidda M, D'Alessio A, Palombi F, Ziparo E, Genazzani AA, Filippini A. NAADP-induced Ca2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae. J Cell Physiol. (2008) 216(2):396-404.
Galli U, Ercolano E, Carraro L, Blasi Roman CR, Sorba G, Canonico PL, Genazzani AA, Tron GC, Billington RA. Synthesis and Biological Evaluation of Isosteric Analogues of FK866, an Inhibitor of NAD Salvage. ChemMedChem. (2008) 3(5);771-9
Billington RA, Genazzani AA, Travelli C, Condorelli F. NAD depletion by FK866 induces autophagy. Autophagy. (2008) 4(3):385-7.
Billington RA, Travelli C, Ercolano E, Galli U, Roman CB, Grolla AA, Canonico PL, Condorelli F, Genazzani AA. Characterization of NAD uptake in mammalian cells. J Biol Chem. (2008) 283(10), 6367-74.
Tron GC, Pirali T, Billington RA, Canonico PL, Sorba G, Genazzani A, Click chemistry reactions in medicinal chemistry: Applications of the 1,3-dipolar cycloaddition between azides and alkynes. Med Res Rev (2008) 28(2), 278-308.
Deaglio S, Vaisitti T, Billington RA, Bergui L, Omede' P, Genazzani AA, Malavasi F. CD38/CD19: a lipid raft-dependent signaling complex in human B cells. Blood. (2007) 109(12), 5390-8.
Billington RA, Genazzani AA. PPADS is a reversible competitive antagonist of the NAADP receptor. Cell Calcium (2007) 41(6), 505-511.
Billington RA, Bellomo EA, Floriddia EM, Erriquez J, Distasi C, Genazzani AA. A transport mechanism for NAADP in a rat basophilic cell line. Faseb J. (2006) 20 (3), 521-3.
Billington RA, Bruzzone S, De Flora A, Genazzani AA, Koch-Nolte F, Ziegler M, Zocchi E. Emerging functions of extracellular pyridine nucleotides. Mol. Med. (2006) 12(11-12), 324-7.
Billington RA, Thuring JW, Conway SJ, Packman L, Holmes AB, Genazzani AA. Production and characterization of reduced NAADP (nicotinic acid-adenine dinucleotide phosphate). Biochem J. 2004 378:275-80.
Billington RA, Ho A, Genazzani AA. Nicotinic acid adenine dinucleotide phosphate (NAADP) is present at micromolar concentrations in sea urchin spermatozoa. J Physiol. 2002 544:107-12.
Bak J, Billington RA, Timar G, Dutton AC, Genazzani AA. NAADP receptors are present and functional in the heart. Curr Biol. 2001 11(12):987-90.