MRC Laboratory of Molecular Biology

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Home Group Leaders A to G Bazbek Davletov
Bazbek Davletov

Molecular mechanisms of vesicle fusion

Ferrari E, Maywood ES, Restani L, Caleo M, Pirazzini M, Rossetto O, Hastings MH, Niranjan D, Schiavo G and Davletov B. (2011)
Re-Assembled Botulinum Neurotoxin Inhibits CNS Functions without Systemic Toxicity
Toxins 3(4),345-55.

Darios F, Niranjan D, Ferrari E, Zhang F, Soloviev M, Rummel A, Bigalke H, Suckling J, Ushkaryov Y, Naumenko N, Shakirzyanova A, Giniatullin R, Maywood E, Hastings M, Binz T and Davletov B.(2010)
SNARE tagging allows step-wise assembly of a multimodular medicinal toxin.
Proc Nat Acad Sci USA 107(42), 18197-201.

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), 1-14.

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, 528-33.

Ruipérez V, Darios F, Davletov B. (2010)
Alpha-synuclein, lipids and Parkinson's disease.
Prog Lipid Res 49(4), 420-8.

Davletov B, Montecucco C. (2010)
Lipid function at synapses.
Curr Opin Neurobiol 20(5), 543-9.

 

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Group Members

  • Dhevahi Niranjan
  • Enrico Ferrari
  • Jason Arsenault
  • Chunjing Gu
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Secretion of neurotransmitters is under tight control in our bodies and abnormalities in this process can lead to various neurological and endocrine disorders. Neurotransmitters are released when secretory vesicles fuse with the plasma membrane in a regulated manner. We investigate proteins and lipids involved in vesicle fusion, in order to uncover the molecular principles that govern secretion. We showed that omega fatty acids and a natural lipid called sphingosine stimulate protein assembly, leading to increased vesicle fusion. We now work on finding lipid-like drug molecules which target these proteins and afford a beneficial regulation of neuronal function. We are also investigating how the protein believed to be responsible for Parkinson's disease can influence neurotransmitter release under normal and pathological conditions. Recently, we conceived the idea that it may be possible to use the stability of the neuronal protein complex for extracellular applications in medicine, since SNARE proteins afford a way of linking functional units by simple mixing. We developed a new, protein clipping technique which allows assembly of functional recombinant units into new products. Now we are working towards improving botulinum neurotoxins for medical use by retargeting them to the required tissues and by making safer versions. Elucidation of the molecular pathways operating in neurotransmitter release will contribute to our understanding of brain function and may facilitate the development of novel tools for medicine and neuroscience research.
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Last Updated on Tuesday, 27 September 2011 14:33