Introduction to the vacant position:
The Nanomalaria Group is looking for an Early Stage Researcher (PhD student) to develop his/her PhD thesis project on the development of new antimalarial drugs. 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 compounds of easy and cost-affordable production, ideally belonging to chemical classes where no antimalarials have been described so far, having several molecular targets in the pathogen and acting through new mechanisms not shared by other currently used drugs. Although potentially toxic protein aggregates are abundant in all malaria parasite stages, the results of our current Plan Nacional project indicate that peptides exacerbating protein aggregation in Plasmodium falciparum do not affect its viability. However, in the same project we have obtained evidence that certain compounds inhibiting the aggregation of proteins are lethal for the pathogen at low nM concentrations. One such compound, the bis(styrylpyridinium) salt YAT2150, the active component of a commercial reagent used to stain protein deposits in live cells, was particularly attractive because of its easy, rapid and inexpensive synthesis and its activity against blood stages of P. falciparum, with an in vitro IC50 of 90 nM. This compound, a potent inhibitor of the aggregation of the amyloid β peptide 1-40, presents no adverse effects in mice up to 10 mg/kg and, because it fluoresces when in contact with Plasmodium, it is a theranostic agent.
The general objective of this project is to explore if the YAT2150-mediated inhibition of protein aggregation can be translated into an antimalarial strategy, which will be achieved through these detailed objectives: (i) to improve the selectivity index of YAT2150 through a targeted delivery strategy based on its encapsulation in immunoliposomes, (ii) to characterize in live Plasmodium cells the role of YAT2150 as protein aggregation inhibitor in both asexual blood stages and in sexual (gametocyte) forms, (iii) to assess the likelihood of resistance evolution in Plasmodium to YAT2150, and (iv) to determine the in vivo antimalarial activity of YAT2150. The results of these concrete objectives will inform about the overarching question of which is the physiological role of protein aggregation in malaria parasites. Because impairing proteostasis potentially targets multiple gene products, rapid evolution of resistance to this drug is unlikely to occur. In addition, YAT2150 belongs to a chemical family where no antimalarials have been described so far, and therefore the parasite will not be able to adapt resistance mechanisms already existing for other drugs.
The results of the characterization of the in vitro activity of the liposome-encapsulated drug, the study of its antimalarial mechanism, and the assessment of its in vivo activity and of the likelihood of the evolution of resistances to it, will be determinant to decide if YAT2150 can enter the preclinical and clinical pipeline leading to its development into a new antimalarial medicine. Taking into account the economic landscape of malaria, certain properties of YAT2150 (high activity against Plasmodium blood stages, relatively low in vivo toxicity, belonging to a new family of antimalarials, cost-efficient synthesis and storage at room temperature for long periods of time), present it as a potentially key actor regarding future efforts leading to malaria eradication.
Main tasks and responsibilities / The successful candidate will develop research involving:
- Encapsulation of antimalarial drugs in targeted nanocarriers
- Characterization of the in vitro and in vivo antimalarial activity of the encapsulated drugs
- Characterization of RNAseq profiles of drug-treated vs. non-treated Plasmodium falciparum cultures.
Requirements for candidates:
- Degree and Master on Biomedical Sciences, Genomics or related field.
- Competencies and skills: Communication, Teamwork and collaboration, Commitment, Proactivity, Integrity, Critical and Analytical thinking.
- High level of English.
- Expertise in cell cultures, confocal fluorescence microscopy, RNAseq and cellular and molecular biology techniques.
- Experience with in vitro cultures of Plasmodium falciparum will be a plus.
- Certificate for the manipulation of laboratory animals (mice) will be a plus.
- Supervision of Master students.
We Offer:
- Number of available positions: 1
- Starting date: November 16, 2022
- Working conditions:
- Full-time contract. 4 years, 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.
- 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:
Until September 30th an online application form is available through IBEC dedicated site: https://careers.ibecbarcelona.eu/
Only those applications submitted before the deadline will be evaluated.
Reference: PhD-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.”
Protection of personal information:
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, 22 research groups and a team of researchers and support services of 350 people from 30 different countries. www.ibecbarcelona.eu
