We are looking for postdoctoral researcher candidates willing to apply to the H2020 MARIE SKŁODOWSKA-CURIE INDIVIDUAL FELLOWSHIPS, to join the Synthetic Biology and Smart Therapeutic and Diagnostic Nanosystems at the Andalusian Centre for Nanomedicine and Biotechnology (BIONAND), a multidisciplinary research group integrated by biotechnologists and clinicians(for more info visit http://www.bionand.es/groups/sbstnl ).
We offer to support the candidate application to a postdoctoral contract within the 2020 MARIE SKŁODOWSKA-CURIE INDIVIDUAL FELLOWSHIPS in its 2019 call (https://ec.europa.eu/info/funding-tenders/opportunities/portal/screen/opportunities/topic-details/msca-if-2019 ), in order to work in the following project:
Evaluation of the in vivo therapeutic efficacy of toxin-antitoxin-based anticancer agents
Background information of the project: The pharmacological treatment of cancer requires developing highly selective inducers of cell death. Classical chemotherapeutic agents are very effective at killing cells but display poor selectivity, and this leads to an excessive collateral damage that limits their efficacy and clinical applicability. Molecularly targeted drugs, directed against oncoproteins to which cancer cells seem to be 'addicted', are more selective than classical chemotherapeutic agents. However, issues like intra-tumoral molecular heterogeneity, cross-talks between different cellular signaling pathways, and the acquisition of therapeutic resistance also limit the efficacy of these agents which, on the other hand, are not always exempt of causing side effects.
To overcome these limitations, our group pursues the development of innovative gene-based therapeutic approaches that merge the killing efficiency of classical chemotherapeutic agents and the cellular selectivity of molecularly targeted drugs. In this context, we have successfully engineered synthetic biological systems that are able of distinguishing cancer cells from normal cells and induce the suicide of the former without damaging the latter. For this, we use a prokaryotic protein, toxin Kid, that triggers apoptosis in human cells, and variants of its cognate neutralizing antitoxin, protein Kis (or its encoding gene), appropriately engineered to make them unstable, and susceptible of rapid degradation, in cancer cells suffering specific oncogenic insults. The resulting systems effectively use predetermined intracellular cancer biomarkers as inducers of their own activation. Using cultured cells, we have demonstrated that these systems trigger the suicide of targeted tumor cells and, at the same time, maintain non-targeted cells protected from collateral damage, thus promoting highly selective cancer cell killing. This approach, which is protected by international patents, can be adapted to respond to a broader variety of oncogenic insults, and offers the opportunity of limiting toxicity to targeted cancer cells, even if healthy cells are also reached by the therapeutic agent upon systemic delivery.
Aim of the project and candidate requirements: Our objective now will be to integrate some of our systems in an appropriate gene delivery vector (preferably, but not exclusively, AAV-derived) and then assess the therapeutic efficacy of the final product in mouse xenografts. In this context, we are seeking to recruit an ambitious postdoctoral researcher keen to work on these developments. Ideal candidates would be individuals with previous experience in the preparation of these type of vectors, their use in animal models, and the development of strategies to reduce their immunogenicity and improve their stability and distribution in vivo.
Description of the PI
Guillermo de la Cueva
Description of the center
The hosting institution has all core facilities required to execute projects of this kind (http://www.bionand.es/core-facilities ), and the recipient lab is integrated by experienced basic and clinical researchers providing the appropriate environment to prepare the proposal and complete the project successfully.
Candidates must meet all the requirements set up by the MSCA-2019 call and be in possession of a competitive CV. Interested applicants must send a copy of their CV to Guillermo de la Cueva Méndez (firstname.lastname@example.org ) before 7th June 2019. Importantly, candidates must include an introductory letter explaining how their previous experience make them suitable for the post, and a one/two page(s) summary of the project that they would like to propose as part of the application.
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