Professor Bazbek Davletov

School of Biosciences

Chair in Biomedical Science

b.davletov@sheffield.ac.uk
+44 114 222 5111

D225, Alfred Denny Building

Full contact details

Professor Bazbek Davletov
School of Biosciences
D225
Alfred Denny Building
Western Bank
Sheffield
S10 2TN

Profile

2012-present: Chair in Biomedical Science, School of Biosciences, University of Sheffield, UK.
1998-2012: Programme Leader, Medical Research Council, The MRC Laboratory of Molecular Biology, Cambridge, UK.
1995-1997: Wellcome Trust Research Fellow, Imperial College, London.
1988-1991: Research Associate, Institute of Bioorganic Chemistry, Moscow.

Rational development of drugs involves understanding molecular principles of the cellular processes one would like to target. I started my career in neurobiology by asking a basic question: What is the molecular machinery that allows neurons to communicate with each other? In the 1980s, scientists knew that neurons release neurotransmitters but the mechanisms of secretion were not known. I used the most potent neuronal secretagogue – a protein called alpha-latrotoxin, the main ingredient of the black widow spider venom – to isolate its neuronal receptors.

These receptors happened to be membrane proteins responsible for interlinking neurons: neurexins and latrophilins. I then investigated in depth synaptic proteins which either bind or are cleaved by neurotoxins: synaptotagmin, syntaxin, SNAP25 and VAMP proteins. These synaptic proteins constitute the fine-tuned release machinery responsible for secretion of neurotransmitters and are the targets of botulinum neurotoxins. My research demonstrated step-by-step protein interactions that are crucial for vesicle fusion and neurotransmitter release.

My work on synaptic proteins and neurotoxins gave rise to several translational ideas, and I engaged top experts to forge fruitful collaborations in cancer, pain and botulinum fields. With Prof. Brindle at Cambridge University, we demonstrated that synaptotagmin protein could be used to indicate success in cancer treatment. With Prof. Hunt at London University, we demonstrated that engineered botulinum molecules could provide long-lasting pain relief in animal models of pain. With Drs Sesardic and Stickings at Medicines and Healthcare products Regulatory Agency, we developed novel neurotoxin detection assays, required to replace animal use in related biomedical fields.

Qualifications

1992-1994: PhD, University of Texas Southwestern Medical Center, Dallas, USA. Supervisor: Prof Thomas Sudhof, Nobel Prize in Physiology and Medicine 2013. 11 joint publications.
1980-1985: BA, MSc in Biochemistry, Moscow State University, Russia.

Research interests

My laboratory is working on the development of new long-lasting pain relief. Around 12% of adults suffer from severe, disabling chronic pain which occurs due to over-reactive neurons. At present, the use of drugs to treat chronic pain is rarely curative and often limited by intolerable side effects. A key feature of our approach is the use of engineered botulinum neurotoxin to selectively silence specific types of neurons for prolonged periods of time. This strategy has evolved from my studies of neuronal communication which universally depends on SNARE proteins.

We demonstrated that specific cleavage of these proteins can lead to a prolonged silencing of neurons with full recovery after several months. My laboratory recently developed a wide range of botulinum molecules with selective actions. Specifically, several of our products target central and sensory neurons but not neuromuscular junctions. This feature makes engineered botulinum molecules more attractive in treating various chronic neuronal disorders since neuronal silencing can be achieved without muscle paralysis.

We investigate botulinum action on SNARE proteins in cell cultures and to that end, we developed new cell-based assays for testing botulinum and tetanus toxins. This is an important biomedical avenue since it will allow saving thousands of mice from lethal tests used by major pharmaceutical companies.
Proving the analgesic potential of novel botulinum products is conducted in collaboration with internationally recognised pain experts to bring the benefits of basic research to clinical practice. We expect that successful botulinum molecules will be helpful in treating different kinds of chronic pain not only in humans but also in animals.

Publications

Show: Featured publications All publications

Featured publications

Journal articles

Andreou AP, Leese C, Greco R, Demartini C, Corrie E, Simsek D, Zanaboni A, Koroleva K, Lloyd JO, Lambru G , Doran C et al (2021) Double-binding botulinum molecule with reduced muscle paralysis: Evaluation in in vitro and in vivo models of migraine. Toxicon, 190, S5-S5.
Maiarù M, Leese C, Certo M, Echeverria-Altuna I, Mangione AS, Arsenault J, Davletov B & Hunt SP (2018) Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice.. Science Translational Medicine, 10(450). View this article in WRRO
Rust A, Doran C, Hart R, Binz T, Stickings P, Sesardic D, Peden AA & Davletov B (2017) A cell line for detection of botulinum neurotoxin type B. Frontiers in Pharmacology, 8, 796-796. View this article in WRRO
Mangione AS, Obara I, Maiarú M, Geranton SM, Tassorelli C, Ferrari E, Leese C, Davletov B & Hunt SP (2016) Nonparalytic botulinum molecules for the control of pain. PAIN, 157(5), 1045-1055. View this article in WRRO
Rust A, Leese C, Binz T & Davletov B (2016) Botulinum neurotoxin type C protease induces apoptosis in differentiated human neuroblastoma cells. Oncotarget, 7, 33220-33228. View this article in WRRO
Rust A, Hassan HHA, Sedelnikova S, Niranjan D, Hautbergue G, Abbas SA, Partridge L, Rice D, Binz T & Davletov B (2015) Two complementary approaches for intracellular delivery of exogenous enzymes. Scientific Reports, 5, 12444-12444. View this article in WRRO
Ferrari E, Gu C, Niranjan D, Restani L, Rasetti-Escargueil C, Obara I, Geranton SM, Arsenault J, Goetze TA, Harper CB , Nguyen TH et al (2013) Synthetic self-assembling clostridial chimera for modulation of sensory functions.. Bioconjug Chem, 24(10), 1750-1759. View this article in WRRO
Arsenault J, Ferrari E, Niranjan D, Cuijpers SAG, Gu C, Vallis Y, O'Brien J & Davletov B (2013) Stapling of the botulinum type A protease to growth factors and neuropeptides allows selective targeting of neuroendocrine cells. Journal of Neurochemistry, 126(2), 223-233.
Arsenault J, Ferrari E, Niranjan D, Cuijpers SAG, Gu C, Vallis Y, O'Brien J & Davletov B (2013) Stapling of the botulinum type A protease to growth factors and neuropeptides allows selective targeting of neuroendocrine cells.. J Neurochem, 126(2), 223-233. View this article in WRRO
Darios F, Niranjan D, Ferrari E, Zhang F, Soloviev M, Rummel A, Bigalke H, Suckling J, Ushkaryov Y, Naumenko N , Shakirzyanova A et al (2010) SNARE tagging allows stepwise assembly of a multimodular medicinal toxin.. Proc Natl Acad Sci U S A, 107(42), 18197-18201.

All publications

Journal articles

Villanueva J, Gimenez-Molina Y, Davletov B & Gutiérrez LM (2022) Vesicle fusion as a target process for the action of sphingosine and its derived drugs. International Journal of Molecular Sciences, 23(3).
Riches-Duit R, Hassall L, Kogelman A, Westdijk J, Rajagopal S, Davletov B, Doran C, Dobly A, Francotte A & Stickings P (2021) Characterisation of tetanus monoclonal antibodies as a first step towards the development of an in vitro vaccine potency immunoassay. Biologicals, 71, 31-41.
Maiarù M, Leese C, Davletov B & Hunt SP (2021) Long-term amelioration of persistent pain states with a novel botulinum–Substance P construct and reinstatement of analgesia with a second injection of the construct. Toxicon, 190, S45-S46.
Andreou AP, Leese C, Greco R, Demartini C, Corrie E, Simsek D, Zanaboni A, Koroleva K, Lloyd JO, Lambru G , Doran C et al (2021) Double-binding botulinum molecule with reduced muscle paralysis: Evaluation in in vitro and in vivo models of migraine. Toxicon, 190, S5-S5.
Andreou AP, Leese C, Greco R, Demartini C, Corrie E, Simsek D, Zanaboni A, Koroleva K, Lloyd JO, Lambru G , Doran C et al (2020) Double-binding botulinum molecule with reduced muscle paralysis : evaluation in in vitro and in vivo models of migraine. Neurotherapeutics. View this article in WRRO
Leese C, Bresnahan R, Doran C, Simsek D, Fellows AD, Restani L, Caleo M, Schiavo G, Mavlyutov T, Henke T , Binz T et al (2020) Duplication of clostridial binding domains for enhanced macromolecular delivery into neurons. Toxicon: X, 5. View this article in WRRO
Gimenez-Molina Y, García-Martínez V, Villanueva J, Davletov B & Gutiérrez LM (2019) Multiple sclerosis drug FTY-720 toxicity is mediated by the heterotypic fusion of organelles in neuroendocrine cells. Scientific Reports, 9(1). View this article in WRRO
Leese C, Maiaru M, Bresnahan R, Binz T, Hunt S & Davletov B (2018) Duplication of neuronal binding domains derived from clostridial neurotoxins greatly enhances intraneuronal delivery of therapeutics. Toxicon, 156, S68-S68.
Maiarù M, Leese C, Certo M, Echeverria-Altuna I, Mangione AS, Arsenault J, Davletov B & Hunt SP (2018) Selective neuronal silencing using synthetic botulinum molecules alleviates persistent pain states. Toxicon, 156, S72-S72.
Davletov B, Leese C, Bresnahan R, Doran C, Balmforth M, Webb M, Turnbull B, Maiaru M & Hunt S (2018) Discovery of novel botulinum pain therapeutics: A binary approach. Toxicon, 156, S20-S20.
Doran C, Rust A, Hart R, Binz T, Stickings P, Sesardic D, Peden AA & Davletov B (2018) An enzymatic reporter cell line for detection of botulinum neurotoxin type B. Toxicon, 156, S25-S25.
Garcia‐Martinez V, Gimenez‐Molina Y, Villanueva J, Darios FD, Davletov B & Gutiérrez LM (2018) Emerging evidence for the modulation of exocytosis by signalling lipids. FEBS Letters, 592(21), 3493-3503. View this article in WRRO
Maiarù M, Leese C, Certo M, Echeverria-Altuna I, Mangione AS, Arsenault J, Davletov B & Hunt SP (2018) Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice.. Science Translational Medicine, 10(450). View this article in WRRO
Rust A, Shah S, Hautbergue G & Davletov B (2018) Burkholderia Lethal Factor 1, a Novel Anti-Cancer Toxin, Demonstrates Selective Cytotoxicity in MYCN-Amplified Neuroblastoma Cells. Toxins, 10(7), 261-261. View this article in WRRO
Broersen K, Ruiperez V & Davletov B (2018) Structural and Aggregation Properties of Alpha-Synuclein Linked to Phospholipase A2 Action. Protein & Peptide Letters, 25(4), 368-378.
Rust A, Doran C, Hart R, Binz T, Stickings P, Sesardic D, Peden AA & Davletov B (2017) A cell line for detection of botulinum neurotoxin type B. Frontiers in Pharmacology, 8, 796-796. View this article in WRRO
Darios FD, Jorgacevski J, Flašker A, Zorec R, García-Martinez V, Villanueva J, Gutiérrez LM, Leese C, Bal M, Nosyreva E , Kavalali ET et al (2017) Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion. Scientific Reports, 7. View this article in WRRO
Davletov B, Hunt S, Mangione S & Andreou A (2016) Nonparalytic botulinum molecules for chronic pain management. Toxicon, 123, S21-S21.
Mavlyutov TA, Duellman T, Kim HT, Epstein ML, Leese C, Davletov BA & Yang J (2016) Sigma-1 receptor expression in the dorsal root ganglion: Reexamination using a highly specific antibody. Neuroscience, 331, 148-157.
Mangione AS, Obara I, Maiarú M, Geranton SM, Tassorelli C, Ferrari E, Leese C, Davletov B & Hunt SP (2016) Nonparalytic botulinum molecules for the control of pain. PAIN, 157(5), 1045-1055. View this article in WRRO
Rust A, Leese C, Binz T & Davletov B (2016) Botulinum neurotoxin type C protease induces apoptosis in differentiated human neuroblastoma cells. Oncotarget, 7, 33220-33228. View this article in WRRO
Dolgacheva LP, Turovskaya MV, Dynnik VV, Zinchenko VP, Goncharov NV, Davletov B & Turovsky EA (2016) Angiotensin II activates different calcium signaling pathways in adipocytes. Archives of Biochemistry and Biophysics, 593, 38-49.
Rust A, Hassan HHA, Sedelnikova S, Niranjan D, Hautbergue G, Abbas SA, Partridge L, Rice D, Binz T & Davletov B (2015) Two complementary approaches for intracellular delivery of exogenous enzymes. Scientific Reports, 5, 12444-12444. View this article in WRRO
Wang T, Martin S, Papadopulos A, Harper CB, Mavlyutov TA, Niranjan D, Glass NR, Cooper-White JJ, Sibarita J-B, Choquet D , Davletov B et al (2015) Control of Autophagosome Axonal Retrograde Flux by Presynaptic Activity Unveiled Using Botulinum Neurotoxin Type A. The Journal of Neuroscience, 35(15), 6179-6194. View this article in WRRO
Arsenault J, Cuijpers SAG, Niranjan D & Davletov B (2014) Unexpected Transcellular Protein Crossover Occurs During Canonical DNA Transfection. Journal of Cellular Biochemistry, 115(12), 2047-2054. View this article in WRRO
Davletov B (2014) A multiple sclerosis drug sheds light on astrocyte biology.. Acta Physiol (Oxf), 212(1), 8-10.
Arsenault J, Cuijpers SAG, Ferrari E, Niranjan D, Rust A, Leese C, O'Brien JA, Binz T & Davletov B (2014) Botulinum protease-cleaved SNARE fragments induce cytotoxicity in neuroblastoma cells.. J Neurochem, 129(5), 781-791. View this article in WRRO
Ferrari E, Gu C, Niranjan D, Restani L, Rasetti-Escargueil C, Obara I, Geranton SM, Arsenault J, Goetze TA, Harper CB , Nguyen TH et al (2013) Synthetic self-assembling clostridial chimera for modulation of sensory functions.. Bioconjug Chem, 24(10), 1750-1759. View this article in WRRO
Shatillo A, Koroleva K, Giniatullina R, Naumenko N, Slastnikova AA, Aliev RR, Bart G, Atalay M, Gu C, Khazipov R , Davletov B et al (2013) Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system.. Neuroscience, 253, 341-349.
Mohrmann R, de Wit H, Connell E, Pinheiro PS, Leese C, Bruns D, Davletov B, Verhage M & Sørensen JB (2013) Synaptotagmin interaction with SNAP-25 governs vesicle docking, priming, and fusion triggering.. J Neurosci, 33(36), 14417-14430.
Arsenault J, Ferrari E, Niranjan D, Cuijpers SAG, Gu C, Vallis Y, O'Brien J & Davletov B (2013) Stapling of the botulinum type A protease to growth factors and neuropeptides allows selective targeting of neuroendocrine cells. Journal of Neurochemistry, 126(2), 223-233.
Arsenault J, Ferrari E, Niranjan D, Cuijpers SAG, Gu C, Vallis Y, O'Brien J & Davletov B (2013) Stapling of the botulinum type A protease to growth factors and neuropeptides allows selective targeting of neuroendocrine cells.. J Neurochem, 126(2), 223-233. View this article in WRRO
García-Martínez V, Villanueva J, Torregrosa-Hetland CJ, Bittman R, Higdon A, Darley-Usmar VM, Davletov B & Gutiérrez LM (2013) Lipid metabolites enhance secretion acting on SNARE microdomains and altering the extent and kinetics of single release events in bovine adrenal chromaffin cells.. PLoS One, 8(9), e75845. View this article in WRRO
Trkov S, Stenovec M, Kreft M, Potokar M, Parpura V, Davletov B & Zorec R (2012) Fingolimod--a sphingosine-like molecule inhibits vesicle mobility and secretion in astrocytes.. Glia, 60(9), 1406-1416.
Davletov B, Ferrari E & Ushkaryov Y (2012) Presynaptic neurotoxins: an expanding array of natural and modified molecules.. Cell Calcium, 52(3-4), 234-240.
Raingo J, Khvotchev M, Liu P, Darios F, Li YC, Ramirez DM, Adachi M, Lemieux P, Toth K, Davletov B & Kavalali ET (2012) VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission.. Nature Neuroscience, 15(5), 738-745. View this article in WRRO
Ferrari E, Soloviev M, Niranjan D, Arsenault J, Gu C, Vallis Y, O'Brien J & Davletov B (2012) Assembly of protein building blocks using a short synthetic peptide.. Bioconjug Chem, 23(3), 479-484.
Ferrari E, Maywood ES, Restani L, Caleo M, Pirazzini M, Rossetto O, Hastings MH, Niranjan D, Schiavo G & Davletov B (2011) Re-assembled botulinum neurotoxin inhibits CNS functions without systemic toxicity.. Toxins (Basel), 3(4), 345-355. View this article in WRRO
Rituper B, Davletov B & Zorec R (2011) Lipid-protein interactions in exocytotic release of hormones and neurotransmitters (vol 5, pg 747, 2010). CLINICAL LIPIDOLOGY, 6(4), 493-494.
Rituper B, Davletov B & Zorec R (2011) Erratum: Lipid-protein interactions in exocytotic release of hormones and neurotransmitters (Clinical Lipidology (2010) 5: 5 (747-761)). Clinical Lipidology, 6(4), 493-494.
Darios F, Niranjan D, Ferrari E, Zhang F, Soloviev M, Rummel A, Bigalke H, Suckling J, Ushkaryov Y, Naumenko N , Shakirzyanova A et al (2010) SNARE tagging allows stepwise assembly of a multimodular medicinal toxin.. Proc Natl Acad Sci U S A, 107(42), 18197-18201.
Ruipérez V, Darios F & Davletov B (2010) Alpha-synuclein, lipids and Parkinson's disease.. Prog Lipid Res, 49(4), 420-428.
Davletov B & Montecucco C (2010) Lipid function at synapses.. Curr Opin Neurobiol, 20(5), 543-549.
Darios F, Ruipérez V, López I, Villanueva J, Gutierrez LM & Davletov B (2010) Alpha-synuclein sequesters arachidonic acid to modulate SNARE-mediated exocytosis.. EMBO Rep, 11(7), 528-533.
Ferrari E, Darios F, Soloviev M & Davletov B (2010) NanoLock polypeptide for the permanent immobilization of recombinant proteins on SNAP25 functionalized supports. European Cells and Materials, 20(SUPPL.3), 80.
Rituper B, Davletov B & Zorec R (2010) Lipid-protein interactions in exocytotic release of hormones and neurotransmitters. Clinical Lipidology, 5(5), 747-761.
Ferrari E, Darios F, Zhang F, Niranjan D, Bailes J, Soloviev M & Davletov B (2010) Binary polypeptide system for permanent and oriented protein immobilization.. J Nanobiotechnology, 8, 9. View this article in WRRO
Connell E, Darios F, Peak-Chew S, Soloviev M & Davletov B (2009) N-terminal acetylation of the neuronal protein SNAP-25 is revealed by the SMI81 monoclonal antibody.. Biochemistry, 48(40), 9582-9589.
Darios F, Wasser C, Shakirzyanova A, Giniatullin A, Goodman K, Munoz-Bravo JL, Raingo J, Jorgacevski J, Kreft M, Zorec R , Rosa JM et al (2009) Sphingosine facilitates SNARE complex assembly and activates synaptic vesicle exocytosis.. Neuron, 62(5), 683-694.
Friedrich R, Groffen AJ, Connell E, van Weering JRT, Gutman O, Henis YI, Davletov B & Ashery U (2008) DOC2B acts as a calcium switch and enhances vesicle fusion.. J Neurosci, 28(27), 6794-6806.
Connell E, Giniatullina A, Lai-Kee-Him J, Tavare R, Ferrari E, Roseman A, Cojoc D, Brisson AR & Davletov B (2008) Cross-linking of phospholipid membranes is a conserved property of calcium-sensitive synaptotagmins.. J Mol Biol, 380(1), 42-50.
Connell E, Scott P & Davletov B (2008) Real-time assay for monitoring membrane association of lipid-binding domains.. Anal Biochem, 377(1), 83-88.
Krishnan AS, Neves AA, de Backer MM, Hu D-E, Davletov B, Kettunen MI & Brindle KM (2008) Detection of cell death in tumors by using MR imaging and a gadolinium-based targeted contrast agent.. Radiology, 246(3), 854-862.
Arunachalam L, Han L, Tassew NG, He Y, Wang L, Xie L, Fujita Y, Kwan E, Davletov B, Monnier PP , Gaisano HY et al (2008) Munc18-1 is critical for plasma membrane localization of syntaxin1 but not of SNAP-25 in PC12 cells.. Mol Biol Cell, 19(2), 722-734.
Darios F, Connell E & Davletov B (2007) Phospholipases and fatty acid signalling in exocytosis.. J Physiol, 585(Pt 3), 699-704.
Berninghausen O, Rahman MA, Silva J-P, Davletov B, Hopkins C & Ushkaryov YA (2007) Neurexin Ibeta and neuroligin are localized on opposite membranes in mature central synapses.. J Neurochem, 103(5), 1855-1863.
Fang W, Wang F, Ji S, Zhu X, Meier HT, Hellman RS, Brindle KM, Davletov B & Zhao M (2007) SPECT imaging of myocardial infarction using 99mTc-labeled C2A domain of synaptotagmin I in a porcine ischemia-reperfusion model.. Nucl Med Biol, 34(8), 917-923.
Jiménez JL & Davletov B (2007) Beta-strand recombination in tricalbin evolution and the origin of synaptotagmin-like C2 domains.. Proteins, 68(3), 770-778.
Davletov B, Connell E & Darios F (2007) Regulation of SNARE fusion machinery by fatty acids.. Cell Mol Life Sci, 64(13), 1597-1608.
Lopez I, Giner D, Ruiz-Nuño A, Fuentealba J, Viniegra S, Garcia AG, Davletov B & Gutiérrez LM (2007) Tight coupling of the t-SNARE and calcium channel microdomains in adrenomedullary slices and not in cultured chromaffin cells.. Cell Calcium, 41(6), 547-558.
Neves AA, Krishnan AS, Kettunen MI, Hu D-E, Backer MMD, Davletov B & Brindle KM (2007) A paramagnetic nanoprobe to detect tumor cell death using magnetic resonance imaging.. Nano Lett, 7(5), 1419-1423.
Davletov B (2007) Conserved prefusion protein assembly in regulated exocytosis. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 146(4), S105-S105.
Connell E, Darios F, Broersen K, Gatsby N, Peak-Chew S-Y, Rickman C & Davletov B (2007) Mechanism of arachidonic acid action on syntaxin-Munc18.. EMBO Rep, 8(4), 414-419.
Broersen K, van den Brink D, Fraser G, Goedert M & Davletov B (2006) Alpha-synuclein adopts an alpha-helical conformation in the presence of polyunsaturated fatty acids to hinder micelle formation.. Biochemistry, 45(51), 15610-15616.
Giniatullin AR, Darios F, Shakirzyanova A, Davletov B & Giniatullin R (2006) SNAP25 is a pre-synaptic target for the depressant action of reactive oxygen species on transmitter release.. J Neurochem, 98(6), 1789-1797.
Darios F & Davletov B (2006) Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3.. Nature, 440(7085), 813-817.
Mahrhold S, Rummel A, Bigalke H, Davletov B & Binz T (2006) The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves.. FEBS Lett, 580(8), 2011-2014.
Yoshida H, Craxton M, Jakes R, Zibaee S, Tavaré R, Fraser G, Serpell LC, Davletov B, Crowther RA & Goedert M (2006) Synuclein proteins of the pufferfish Fugu rubripes: sequences and functional characterization.. Biochemistry, 45(8), 2599-2607.
Rickman C, Jiménez JL, Graham ME, Archer DA, Soloviev M, Burgoyne RD & Davletov B (2006) Conserved prefusion protein assembly in regulated exocytosis.. Mol Biol Cell, 17(1), 283-294.
Davletov B, Bajohrs M & Binz T (2005) Beyond BOTOX: advantages and limitations of individual botulinum neurotoxins. American Journal of Ophthalmology, 140(6), 1173-1173.
Bajohrs M, Darios F, Peak-Chew S-Y & Davletov B (2005) Promiscuous interaction of SNAP-25 with all plasma membrane syntaxins in a neuroendocrine cell.. Biochem J, 392(Pt 2), 283-289.
Davletov B, Bajohrs M & Binz T (2005) Beyond BOTOX: advantages and limitations of individual botulinum neurotoxins.. Trends Neurosci, 28(8), 446-452.
Rickman C, Hu K, Carroll J & Davletov B (2005) Self-assembly of SNARE fusion proteins into star-shaped oligomers.. Biochem J, 388(Pt 1), 75-79.
Rickman C & Davletov B (2005) Arachidonic acid allows SNARE complex formation in the presence of Munc18.. Chem Biol, 12(5), 545-553.
Bajohrs M, Rickman C, Binz T & Davletov B (2004) A molecular basis underlying differences in the toxicity of botulinum serotypes A and E.. EMBO Rep, 5(11), 1090-1095.
Choi W, Zibaee S, Jakes R, Serpell LC, Davletov B, Crowther RA & Goedert M (2004) Mutation E46K increases phospholipid binding and assembly into filaments of human alpha-synuclein.. FEBS Lett, 576(3), 363-368.
Jung H-I, Kettunen MI, Davletov B & Brindle KM (2004) Detection of apoptosis using the C2A domain of synaptotagmin I.. Bioconjug Chem, 15(5), 983-987.
Rickman C, Archer DA, Meunier FA, Craxton M, Fukuda M, Burgoyne RD & Davletov B (2004) Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate.. J Biol Chem, 279(13), 12574-12579.
Rickman C, Craxton M, Osborne S & Davletov B (2004) Comparative analysis of tandem C2 domains from the mammalian synaptotagmin family.. Biochem J, 378(Pt 2), 681-686.
Hu K, Rickman C, Carroll J & Davletov B (2004) A common mechanism for the regulation of vesicular SNAREs on phospholipid membranes.. Biochem J, 377(Pt 3), 781-785.
Rickman C, Meunier FA, Binz T & Davletov B (2004) High affinity interaction of syntaxin and SNAP-25 on the plasma membrane is abolished by botulinum toxin E.. J Biol Chem, 279(1), 644-651.
Davletov B & Jiménez JL (2004) Sculpting a domain by splicing.. Nat Struct Mol Biol, 11(1), 4-5.
Foran PG, Davletov B & Meunier FA (2003) Getting muscles moving again after botulinum toxin: novel therapeutic challenges.. Trends Mol Med, 9(7), 291-299.
Rickman C & Davletov B (2003) Mechanism of calcium-independent synaptotagmin binding to target SNAREs.. J Biol Chem, 278(8), 5501-5504.
Hu K & Davletov B (2003) SNAREs and control of synaptic release probabilities.. FASEB J, 17(2), 130-135.
Hu K, Carroll J, Rickman C & Davletov B (2002) Action of complexin on SNARE complex.. J Biol Chem, 277(44), 41652-41656.
Hu K, Carroll J, Fedorovich S, Rickman C, Sukhodub A & Davletov B (2002) Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion.. Nature, 415(6872), 646-650.
Zhao M, Beauregard DA, Loizou L, Davletov B & Brindle KM (2001) Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent.. Nat Med, 7(11), 1241-1244.
Ashton AC, Rahman MA, Volynski KE, Manser C, Orlova EV, Matsushita H, Davletov BA, Van Heel M, Grishin EV & Ushkaryov YA (2000) Tetramerisation of α-latrotoxin by divalent cations is responsible for toxin-induced non-vesicular release and contributes to the Ca²⁺-dependent vesicular exocytosis from synaptosomes. Biochimie, 82(5), 453-468.
Rahman MA, Ashton AC, Meunier FA, Davletov BA, Dolly JO & Ushkaryov YA (1999) Norepinephrine exocytosis stimulated by α-latrotoxin requires both external and stored Ca²⁺ and is mediated by latrophilin, G proteins and phospholipase C. Philosophical Transactions of the Royal Society B: Biological Sciences, 354(1381), 379-386.
Davletov B, Perisic O & Williams RL (1998) Calcium-dependent membrane penetration is a hallmark of the C2 domain of cytosolic phospholipase A2 whereas the C2A domain of synaptotagmin binds membranes electrostatically.. J Biol Chem, 273(30), 19093-19096.
Davletov BA, Meunier FA, Ashton AC, Matsushita H, Hirst WD, Lelianova VG, Wilkin GP, Dolly JO & Ushkaryov YA (1998) Vesicle exocytosis stimulated by α-latrotoxin is mediated by latrophilin and requires both external and stored Ca²⁺. EMBO Journal, 17(14), 3909-3920.
Lelianova VG, Davletov BA, Sterling A, Rahman MA, Grishin EV, Totty NF & Ushkaryov YA (1997) α-Latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. Journal of Biological Chemistry, 272(34), 21504-21508.
Shao X, Davletov BA, Sutton RB, Südhof TC & Rizo J (1996) Bipartite Ca²⁺-binding motif in C2 domains of synaptotagmin and protein kinase C. Science, 273(5272), 248-251.
Davletov BA, Shamotienko OG, Lelianova VG, Grishin EV & Ushkaryov YA (1996) Isolation and biochemical characterization of a Ca²⁺-independent α- latrotoxin-binding protein. Journal of Biological Chemistry, 271(38), 23239-23245.
Sutton RB, Davletov BA, Berghuis AM, Sudhof TC & Sprang SR (1995) Structure of the first C2 domain of synaptotagmin I: A novel Ca²⁺/phospholipid-binding fold. Cell, 80(6), 929-938.
Davletov BA, Krasnoperov V, Hata Y, Petrenko AG & Sudhof TC (1995) High affinity binding of α-latrotoxin to recombinant neurexin Iα. Journal of Biological Chemistry, 270(41), 23903-23905.
Li C, Davletov BA & Südhof TC (1995) Distinct Ca²⁺ and Sr²⁺ binding properties of synaptotagmins: Definition of candidate Ca²⁺ sensors for the fast and slow components of neurotransmitter release. Journal of Biological Chemistry, 270(42), 24898-24902.
Zhang JZ, Davletov BA, Südhof TC & Anderson RGW (1994) Synaptotagmin I is a high affinity receptor for clathrin AP-2: Implications for membrane recycling. Cell, 78(5), 751-760.
Davletov BA & Sudhof TC (1994) Ca²⁺-dependent conformational change in synaptotagmin I. Journal of Biological Chemistry, 269(46), 28547-28550.
Davletov B, Sontag JM, Hata Y, Petrenko AG, Fykse EM, Jahn R & Südhof TC (1993) Phosphorylation of synaptotagmin I by casein kinase II.. J Biol Chem, 268(9), 6816-6822.
Hata Y, Davletov B, Petrenko AG, Jahn R & Südhof TC (1993) Interaction of synaptotagmin with the cytoplasmic domains of neurexins.. Neuron, 10(2), 307-315.
Davletov BA & Sudhof TC (1993) A single C2 domain from synaptotagmin I is sufficient for high affinity Ca²⁺/phospholipid binding. Journal of Biological Chemistry, 268(35), 26386-26390.
Geppert M, Ushkaryov YA, Hata Y, Davletov B, Petrenko AG & Südhof TC (1992) Neurexins.. Cold Spring Harb Symp Quant Biol, 57, 483-490.
Petrenko AG, Perin MS, Davletov BA, Ushkaryov YA, Geppert M & Südhof TC (1991) Binding of synaptotagmin to the α-latrotoxin receptor implicates both in synaptic vesicle exocytosis. Nature, 353(6339), 65-68.
aldashev AA, Borbugulov UM, Davletov BA & Meǐmanaliev TS (1989) Changes in the adrenoreceptor function in mountaineers with right ventricular hypertrophy. Fiziologiia cheloveka, 15(6), 138-140.
Aldashev AA, Borbugulov UM, Davletov BA & Mirrakhimov MM (1989) Human adrenoceptor system response to the development of high altitude pulmonary arterial hypertension. Journal of Molecular and Cellular Cardiology, 21(SUPPL. 1), 175-179.
Sikorra S, Skiba M, Dorner M, Weisemann J, Weil M, Valdezate S, Davletov B, Rummel A, Dorner B & Binz T () Botulinum Neurotoxin F Subtypes Cleaving the VAMP-2 Q58–K59 Peptide Bond Exhibit Unique Catalytic Properties and Substrate Specificities. Toxins, 10(8), 311-311. View this article in WRRO
Rust A, Partridge L, Davletov B & Hautbergue G () The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations. Toxins, 9(11), 344-344. View this article in WRRO

Conference proceedings papers

Abdullahi RA, Lloyd J, Jones M, Lambru G, Al-Kaisy A, Davletov B & Andreou A (2019) Long term actions of a recombinant advanced Botulinum toxin (BiTox-AA) molecule in migraine animal models. CEPHALALGIA, Vol. 39 (pp 230-230)
AbuukarAbdullahi R, Lloyd JO, Jones MG, Lambru G, Al-Kaisy A, Davletov B & Andreou AP (2018) Long-term effects of the non-paralytic botulinum toxin A molecule BiTox in migraine animal models. JOURNAL OF HEADACHE AND PAIN, Vol. 19
Andreou AP, AbuukarAbdullahi R, Lloyd JO, Jones M, Lambru G, Al-Kaisy A & Davletov B (2018) Long-term Effects of the Non-paralytic Botulinum Toxin a Molecule Bitox in a Migraine Animal Model. HEADACHE, Vol. 58(8) (pp 1335-1336)
Ma W, Aboagye-Mensah D, Soloviev M, Davletov B & Ferrari E (2017) Protein Conjugation to Nanoparticles by Designer Affinity Tags. Materials Today: Proceedings, Vol. 4(7) (pp 6923-6929)
Paraskevopoulou M, Perez JT, Miedzik A, Chamberlain J, Lambru G, Davletov B & Andreou AP (2016) NON-PARALYTIC BOTULINUM MOLECULES FOR THE CONTROL OF MIGRAINE. CEPHALALGIA, Vol. 36 (pp 135-135)
Wang T, Martin S, Papadopulos A, Harper C, Mavlyutov T, Niranjan D, Glass N, Cooper-White J, Sibarita J-B, Choquet D , Davletov B et al (2015) Control of autophagosome axonal retrograde flux by presynaptic activity unveiled using botulinum neurotoxin type-A. JOURNAL OF NEUROCHEMISTRY, Vol. 134 (pp 165-165)
Torres-Perez JV, Chamberlain J, Miedzik AA, Nagy I, Davletov B & Andreou AP (2015) Non-paralytic botulinum chimeras increase the activation threshold of the trigeminovascular system in migraine models. CEPHALALGIA, Vol. 35 (pp 4-4)
Arsenault J, Ferrari E, Niranjan D & Davletov B (2013) On-Demand Assembly of Macromolecules Used for the Design and Application of Targeted Secretion Inhibitors. Peptides Across the Pacific: The Proceedings of the Twenty-Third American and the Sixth International Peptide Symposium
Arsenault J, Cuijpers SAG, Ferrari E, Niranjan D, O'Brien JA & Davletov B (2013) Cleaved Intracellular SNARE Peptides are Implicated in a Novel Cytotoxicity Mechanism of Botulinum Serotype C. Peptides Across the Pacific: The Proceedings of the Twenty-Third American and the Sixth International Peptide Symposium
Arsenault J, Ferrari E, Niranjan D & Davletov B (2012) Retargeted Botulinum Neurotoxins using SNARE protein stapling capable of selectively silencing neuroendocrine cells. JOURNAL OF PEPTIDE SCIENCE, Vol. 18 (pp S154-S154)
Mohrmann R, De Wit H, Connell E, Davletov B, Verhage M & Sørensen JB (2011) Functional Characterization of Putative Synaptotagmin-Binding Interfaces in SNAP-25. Biophysical Journal, Vol. 100(3) (pp 407a-407a)
Arsenault J, O'Brien J, Ferrari E, Niranjan D, Ruiperez V & Davletov B (2011) SNARE based peptide linking as an efficient strategy to retarget botulinum neurotoxin's enzymatic domain to specific neurons using diverse neuropeptides as targeting domains. BIOPOLYMERS, Vol. 96(4) (pp 466-466)
Broersen K & Davletov B (2007) Lipids and alpha-synuclein aggregation in Parkinson's disease. MOVEMENT DISORDERS, Vol. 22(12) (pp VI-VI)
Voigl B, Hlavacka A, Craxton M, Davletov B, Menzel D & Baluska F (2005) Plant Synaptotagmins: effectors of calcium-regulated endocytosis and exocytosis in plants?. EUROPEAN JOURNAL OF CELL BIOLOGY, Vol. 84 (pp 131-131)
Bajohrs M, Rickman C, Binz T & Davletov B (2004) The interaction of SNAP-25 with syntaxin1 and syntaxin2 accounts for the differential toxicity of botulinum toxin A and E. MOLECULAR BIOLOGY OF THE CELL, Vol. 15 (pp 71A-71A)

Research group

Group members:

Charlotte Leese, Postdoctoral Fellow
Ciara Doran, Postdoctoral Fellow
Claire Christmas, Postdoctoral Fellow
Deniz Simsek, PhD Student
Eve Corrie, PhD Student
Tatum Askey, MSc Student

Collaborators:

Stephen Hunt (University College London)
Rashid Giniatullin (University of Kuopio, Finland)
Paul Stickings (National Institute for Biological Standards and Control, London)
Silvia Fragoeira, Merck Animal Health
Ron Broide, Allergan

Grants

Medical Research Council
NC3R

Teaching activities

Undergraduate and postgraduate taught modules

BMS109 Introduction to Biomedical Science
BMS110 Research Topics in Biomedicine
BMS242/243 Cell & Molecular Biology
BMS349 Dissertation module
BMS397 Laboratory projects
BMS401/6051 Masters course
BMS402/6052 Laboratory projects
BMS403/6053 Critical Analysis of Current Science