Introduction to the vacant position:
The Nanomalaria Group is looking for a highly qualified researcher with a synthetic chemistry background and expertise in biological evaluations, particularly in Plasmodium falciparum cultures and the cellular biology of malaria parasites. The contract will be within the framework of one of the research lines of the Nanomalaria Group, whose objective is the characterization of the inhibition of protein aggregation as a novel mode of action of future antimalarial drugs.
The available arsenal of antimalarial drugs is insufficient to progress towards eradication of the disease, a scenario that is worsened by the rampant evolution of resistance by Plasmodium. This situation calls for immediate efforts to discover new antimalarials of easy and cost-affordable production, having several molecular targets in the pathogen and acting through new antiparasitic mechanisms not shared by currently used drugs.
The bis(styrylpyridinium) salt YAT2150 has a number of properties that make it highly interesting as antimalarial drug, namely: (i) its synthesis is easy and rapid (only two steps), which results in an attractive activity/cost ratio taking into account that its main clinical deployment would be in the low per capita income regions where malaria is endemic; (ii) its mode of action (inhibition of protein aggregation in the parasite) presumably targets multiple proteins, which would likely prevent a rapid resistance evolution by the pathogen, as opposed to most other current antimalarial drugs which target products of one or a few genes; (iii) it belongs to an unexplored chemical family where no other antimalarial has been described up to date, which will prevent the adaptation by the parasite of preexisting resistance mechanisms to currently used drugs; (iv) our preliminary data suggest that YAT2150 might be active against all Plasmodium species causing human malaria, which would make of this drug a pan-malaria treatment; (v) this molecule fluoresces when interacting with its molecular targets in Plasmodium cells, which makes of it a theranostic agent; (vi) it targets (binds) all stages of the parasite in the vertebrate host and in the mosquito vector; (vii) the compound has a long shelf life (months) at room temperature; (viii) it has a low parasite in vitro growth half-maximal inhibitory concentration (IC50) below 100 nM. These characteristics place YAT2150 as a highly promising model for a new generation of antimalarial drugs for the post-artemisinin era, since resistances to this last drug (on which the main current therapeutic approaches are based) are widespread in Asia, and resistance markers have been already identified in Africa and South America.
However, the 50% cytotoxic concentration (CC50) of YAT2150 for human cells results in a selectivity index (SI: CC50/IC50) below 100. The perspectives of a successful clinical development of YAT2150 as antimalarial drug will improve significantly if the SI can be incremented to values above 100.
Main objective of the project: To obtain YAT2150 derivatives with a sufficiently favorable selectivity index in order to allow this new family of antimalarial drugs entering the preclinical development pipeline.
Specific objectives of the project: (i) To synthesize YAT2150 chemical derivatives through the selective modification of different chemical groups in the parent molecule. These derivatives will be initially evaluated for their activity as inhibitors of protein aggregation in vitro and in live Plasmodium falciparum cultures. (ii) Characterization of the activity of the derivatives in in vitro P. falciparum cultures and in human cell cultures in order to obtain the respective IC50 and CC50 and calculate the corresponding SI. Finally (iii), for the derivatives with higher SI, in vivo assays in a murine model of malaria will assess the potential of those compounds for entering a preclinical development process.
The successful candidate will develop research involving:
- Synthesis of YAT2150 derivatives
- Antiplasmodial in vitro activity characterization of YAT2150 derivatives
- In vivo activity characterization of YAT2150 derivatives in a murine model of malaria
Requirements for candidates:
- Degree and MSc in Pharmacy, Chemistry, Pharmaceutical Chemistry or similar areas.
- Experience in chemical synthesis.
- Experience in biological screening of bioactive compounds.
- Experience with in vitro cultures of Plasmodium falciparum will be a plus.
- Competencies and skills: Communication, Teamwork and collaboration, Commitment, Proactivity, Integrity, Critical and Analytical thinking.
- High level of English.
- Certificate for the manipulation of laboratory animals (mice) will be a plus.
We Offer:
- Number of available positions: 1
- Starting date: as soon as possible
- Working conditions:
- Full-time contract for 17 months.
- Very competitive salary
- Measures to reconcile work and family life (maternity and paternity leave, flexible schedule working hours, teleworking, 23 working days of paid holidays, 9 leave days for personal matters, among others).
- IBEC ensures equality of access to professional development opportunities irrespective of employment status, length at IBEC or other factors. The IBEC’s yearly training catalogue offers a wide range of training in technical and transferable skills including mobility grants and a Mentoring programme for predoctral and postdoctoral researchers.
- Stimulating, interdisciplinary research and high-quality international scientific environment.
- Induction programme to facilitate incorporation at IBEC and additional support is provided for foreigners to obtain Visa-working permit and to install in Barcelona.
How to apply:
Only those applications submitted before the deadline will be evaluated.
Until March 3rd an online application form is available through IBEC dedicated site: https://careers.ibecbarcelona.eu/
Reference: PD-XF.
If you have any further question regarding your application, please contact us at jobs@ibecbarcelona.eu
Principles of the selection process:
IBEC is committed to the principles of the Code of Conduct for the Recruitment of Researchers of the European Commission and the Open, Transparent and Merit based Recruitment principles (OTM-R).
IBEC´s Commitment on equal opportunity:
Our strength and excellence as an international transdisciplinary Research Institute are based on diversity. Being an equal opportunity employer, we are committed to diversity and inclusion, so that we support employees irrespective of their gender, nationality, religion, disabilities, age, sexual identity or cultural and socioeconomic background.”
For Postdoctoral and JR GL positions:
IBEC aims for a representative gender balance at all levels of staff, so we strongly encourage women to apply. At least 40% of shortlisted applicants invited to interview have to be women with comparable level of CVs as the male candidates.
Protection of personal data:
IBEC guarantees that candidates’ personal data are processed in accordance with the requirements of the EU General Data Protection Regulation (GDPR) and Law 3/2018 on Data Protection.
Personal data will be processed solely for the purposes of the selection process.
Who we are?
The Institute for Bioengineering of Catalonia, IBEC is an interdisciplinary research center focused on Bioengineering and Nanomedicine based in Barcelona. IBEC is one of the top research institutions named as a Severo Ochoa Research Centre by the Ministry of Science, Universities and Innovation, which recognizes excellence at the highest international level in terms of research, training, human resources, outreach and technology transfer.
IBEC’s mission is to develop international high-quality interdisciplinary research that, while creating knowledge, contributes to making a better quality of life, improving health and creating wealth. A close link with key universities, reference hospitals and corporations, are assets that facilitate achieving the mission.
IBEC was established in 2005 by the Generalitat de Catalunya (Autonomous Government of Catalonia), the University of Barcelona (UB) and the Technical University of Catalonia (UPC).
IBEC is located within the Barcelona Science Park and is managing 3.800 square meters facilities, with an annual budget of 13 Mio€; 3.800 square meters of facilities; 21 research groups and a team of researchers and support services of 350 people from 30 different countries. www.ibecbarcelona.eu
