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Development and validation of new tools to dissect the molecular functions of caspases in non-apoptotic scenarios.

  • Full or part time
    Dr L A Baena-López
  • Application Deadline
    Friday, January 10, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

The apoptotic function of caspases has overshadowed other important roles linked to these evolutionary conserved enzymes during many years. However this unidimensional perspective is rapidly changing. Furthermore, it is becoming clear that caspases are instrumental for the proper regulation of other cellular processes, beyond cell death. These newly identified non-apoptotic roles appear to be highly diverse in many cell types, including stem cells. However the molecular regulation and activity of caspases in non-apoptotic scenarios is poorly understood. This gap knowledge is due to the fact that not many proteins regulators and substrates of caspase activity are uncovered in non-apoptotic contexts.
This project will aim to create and validate a new genetically encoded tool that could facilitate the identification of new partners and substrates of apical caspases in Drosophila and mammalian cells. These tools will combine a template of different caspase members with a modified version of biotin ligases such as BirA or Apex. Upon caspase activation, it is expected that Bir-A would efficiently label those proteins in close proximity to different caspase members. Subsequent mass-spectrometry is expected to uncover the interactome of several caspases members in different tissues and experimental situations. If work, these new tools could help to better define the molecular function and regulation of caspases in non-apoptotic scenarios.
The project will provide training in molecular cloning, cell culture, basic biochemistry (western blot), immunoprecipitation, immunohistochemistry, confocal microscopy (potentially super resolution imaging) and sample preparation for mass-spectrometry. These experiments will be complemented with functional assays performed in flies that will provide training in Drosophila genetics. Genome engineering protocols could be also needed to make the functional characterisation of novel caspase partners during the development as well as in pathological cellular contexts such as tumours.
The experimental work would be done within a friendly and multicultural team, where everybody receives help and support from others, but also under the umbrella of one of the most prestigious Institution in the world (Dunn School of Pathology, University of Oxford). These factors collectively ensure a unique environment to complete an enjoyable and successful PhD.

Funding Notes

4 Year DPhil Prize Studentships cover University fees, a tax free stipend of ~£17,009 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.

References

Learning on the fly: The interplay between Caspases and Cancer
Xu DC, Arthurton L, Baena-Lopez LA. Biomed. Research International. 2018 March 14. [Epub ahead of print]


Non-apoptotic Caspase regulation of stem cell properties.
Baena-Lopez LA, Arthurton L, Xu DC, Galasso A.
Semin Cell Dev Biol. 2017 Nov 1. [Epub ahead of print]


Caspase-dependent activation of Hedgehog-signalling sustains proliferation and differentiation of ovarian somatic stem cells.
Alessia Galasso, Daria Iakovleva, LA. Baena-Lopez. BioRxiv. 2019 August. doi:

Non-apoptotic caspase-dependent regulation of enteroblast quiescence in Drosophila
Lewis Arthurton, Dominik Antoni Nahotko, Jana Alonso, Luis Alberto Baena-Lopez
bioRxiv 707380; doi:

How good is research at University of Oxford in Biological Sciences?

FTE Category A staff submitted: 223.80

Research output data provided by the Research Excellence Framework (REF)

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