Monthly Lab Focus – Davletov Group

Group members

Principal Investigator:

Postdocs:

  • Charlotte Leese
  • Ciara Doran

PhD students:

  • Aleksander Rust
  • Rosalyn Hart
  • Rebecca Bresnahan

Lab manager:

  • Jackie Price

Technician:

  • Deepa Bliss

MSc Students:

  • Muna Nuh Ali, MSc Student
  • Sajid Shah, MSc Student

Daveltove lab group

SPECIALISED CELL DEVELOPMENTScientific Questions we are addressing:

  • Targeting technologies for drug delivery
  • Mechanisms of botulinum neurotoxins action on neurons
  • Design of non-paralysing botulinum constructs for long-lasting pain alleviation
  • Targeting protein translation in cancer and chronic pain
  • Design of multifunctional biomolecules 

Techniques we use:

  • Bacterial protein expression and purification
  • Protein modification and stapling reactions
  • Cell culture and cell labelling
  • Cell death and neurite outgrowth assays
  • Dorsal root ganglion neuronal cultures
  • Fluorescence microscopy analysis of neurons and neuroblastoma cells
  • In vivo tests of new non-paralysing constructs

Mouse sensory neurons in culture

P75_Ganglioside

GT1bgreenSNAP25red_DRG

Images courtesy of Davletov lab 2015.

Lay Summary of research within the lab

We are developing new technologies for delivery of biomedicinal enzymes into neurons. Neuronal disorders are a huge burden to our society and include many untreatable conditions such as chronic pain, epilepsy and neurodegeneration. We recently introduced a ‘protein stapling’ technique which potentially allows conjugation of any therapeutic enzyme to any proven cell-targeting agent. The advantage of this system is that it can incorporate other functionalities such as multiple targeting or endosome-disrupting agents. 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.

Impact

Our novel biomolecular constructs for long-lasting control of pain attracted attention of national and international press and radio. Notably:

Selected Recent Publications:

Student awards/prizes

  • 2015 – BMS Third year PhD symposium award by Aleks Rust
  • 2015 – BMS First year PhD symposium award by Rose Hart
  • 2015 – BMS PhD retreat 3rd place poster award by Rose Hart

Funding:

  • Medical Research Council
  • BBSRC
  • NC3R

Collaborators:

  • Stephen Hunt (University College London)
  • Frederic Meunier (University of Brisbane, Australia)
  • Robert Zorec (University of Ljubljana, Slovenia)
  • Rashid Giniatullin (University of Kuopio, Finland)
  • Thea Sesardic (National Institute for Biological Standards and Control, London)