Professor Bazbek Davletov
Chair in Biomedical Science
Department of Biomedical Science
Room D225 Alfred Denny building
Brief career history
We routinely generate new secretion- and translation-inhibiting biomedicines and characterise their functional effects on primary sensory neurons. Successful targeting and delivery into neurons will pave the way for utilization of known potent enzymes in treatment of neurological disorders. In addition, the results of this study will be important for the design of new multifunctional therapies encompassing antibodies, their fragments, small molecule drugs and siRNAs.
Images courtesy of Davletov lab 2015
A detailed description of my projects:
Project 1: Developing long-lasting analgesic drugs
We plan to obtain evidence in cell cultures that RSPs can block release of pain-signalling molecules from pain-conducting neurons and then to test RSPs for their ability to influence sensory biology in rodent models. Proving the analgesic potential of specific RSP versions will be required to bring the benefits of basic research to clinical practice. We expect that successful RSP molecules will be helpful in treating different kinds of chronic pain not only in humans but also in animals.
Project 2: Targeting translation in cancer treatment
Translation-inhibiting enzymes (Tie-s) is an emerging class of anti-cancer drugs provided they can be targeted into the cytosol of specific cancer cells. Generally, targeting can be achieved by attaching Tie-s to antibodies, growth factors or other ligands which preferentially bind to cancer cells. The anti-proliferative enzymatic activity of Tie-s, however, can only take place in the cytosol which is protected by cellular membranes. Following binding to cancer cells, Tie-s will be processed in the endosomal-lysosomal pathway. To escape degradation, Tie-s must be able to rapidly exit endosomes into the cellular cytosol.
We recently introduced a ‘protein stapling’ technique which potentially allows conjugation of any cancer-inhibiting enzyme to any proven cell-targeting agent. The advantage of this system is that the staple itself can serve as a point where we can add further functionality, such as endosomal escape. Several peptides have been developed which can break endosomes allowing access into the cell interior. Our ‘protein stapling’ system provides a unique opportunity to combine endosome breaking agents with translation-inhibiting and cell-targeting proteins. Successful targeting of functional Tie-s will pave the way for utilization of these potent enzymes in cancer treatment. In addition, the results of this study will be important for the design of new multifunctional cancer therapies encompassing antibodies, their fragments, enzymes and siRNAs.
Undergraduate and postgraduate taught modules
Postgraduate PhD Opportunities
We advertise PhD opportunities (Funded or Self-Funded) on FindAPhD.com
For further information and details of other projects on offer, please see the department PhD Opportunities page:
- Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice.. Science Translational Medicine, 10(450). View this article in WRRO
- A cell line for detection of botulinum neurotoxin type B. Frontiers in Pharmacology, 8, 796-796. View this article in WRRO
- Nonparalytic botulinum molecules for the control of pain. PAIN, 157(5), 1045-1055. View this article in WRRO
- Botulinum neurotoxin type C protease induces apoptosis in differentiated human neuroblastoma cells. Oncotarget, 7, 33220-33228. View this article in WRRO
- Two complementary approaches for intracellular delivery of exogenous enzymes. Scientific Reports, 5, 12444-12444. View this article in WRRO
- Synthetic self-assembling clostridial chimera for modulation of sensory functions.. Bioconjug Chem, 24(10), 1750-1759. View this article in WRRO
- 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
- SNARE tagging allows stepwise assembly of a multimodular medicinal toxin.. Proc Natl Acad Sci U S A, 107(42), 18197-18201.
- Alpha-synuclein sequesters arachidonic acid to modulate SNARE-mediated exocytosis.. EMBO Rep, 11(7), 528-533.
- Binary polypeptide system for permanent and oriented protein immobilization.. J Nanobiotechnology, 8, 9. View this article in WRRO