Oferta de trabajo: Predoctoral researcher at the Nanomalaria research group

Descripción

The Barcelona Institute for Global Health (ISGlobal) is a cutting-edge institute addressing global public health challenges through research, translation into policy and education. ISGlobal has a broad portfolio in communicable and non-communicable diseases including environmental and climate determinants, and applies a multidisciplinary scientific approach ranging from the molecular to the population level. Research is organized in the following main areas, Urban Health and Child and environmental health, Climate & Non-Communicable Diseases, Malaria and other Infectious Diseases, Maternal, Child and reproductive Health.  ISGlobal is accredited with the Severo Ochoa distinction, a seal of excellence of the Spanish Science Ministry.

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.

Lugar

Barcelona

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: January 2023.
  • 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).
  • Stimulating, interdisciplinary research and high-quality international scientifi environment.

 

How to apply

Applicants must fill in the  request form  and include the following code reference
position: PhD_IBEC_Nanomalaria_Sep22, attach the CV and a Cover Letter. Each attached
document must be named with the candidate name and surname. 
The receipt of applications will be open until 9th October 2022. 

Applications will be accepted until 17.00 CET of the closing date.

Only the applications submitted through the request form will be considered.

Only shortlisted candidates will be contacted.

The interviews could be placed during the reception candidatures period.

Diverse candiddacies are welcome, that includes: gender, race, ethnicity, religion, age, sexual
orientation, physical abilities, and political views.

In ISGlobal we are committed to maintaining and developing a work environment in which the values and principles of our organization are respected and equal opportunities between women and men be promoted in each of the areas in which we operate, not tolerating discrimination based on criteria such as age, gender, marital status, race, ethnicity, functional diversity, political leanings, religion, sexual orientation, gender identity or gender expression.

ISGlobal supports the initiative #ScienceforUkraine. Therefore, to sustain Ukraine’s presence in the European Research Area and international scholarly community, candidates from Ukraine on all levels of scholarly career are welcome: students, PhD candidates, early career researchers and senior scholars.

We confirm our commitment towards the value of the diversity of our staff and student population and seek to promote peace, equity, diversity and inclusion as essential elements in contribution to improving health worldwide.