Specific targeting of parasites and bacteria with DNA aptamers

Group: Nanomalaria and Bacterial infections: antimicrobial therapies
Group leader: Xavier Fernàndez-Busquets (jfernandez@ibecbarcelona.eu) and Eduard Torrents (etorrents@ibecbarcelona.eu)

Research project

Antibiotics and antiparasitic agents are increasingly failing due to the evolution of resistance to them by their target pathogens, notably protozoan parasites and bacteria like Plasmodium, Leishmania, Pseudomonas aeruginosa and Staphylococcus aureus. As a result, the rhythm at which new antimicrobial compounds are entering clinical use is slower than the speed at which they are becoming useless due to the appearance of resistant strains. A solution to this problem is to make more efficient the few active antimicrobial drugs that we have today while planning for better use of future ones to be discovered. This can be achieved by encapsulating them in nanocarriers targeted to the parasite or bacterial cells, which will increase the local amounts being delivered to the pathogens, boosting in this way the efficacy of the medicines. In turn, this specific targeting will reduce overall administration, thus minimizing costs and potential side effects (toxicity) in the patient since a much lower dose will be required to kill the infectious agents rapidly and thus significantly reduce resistance evolution. Taking advantage of the ample expertise of the Nanomalaria and the Bacterial Infections and Antimicrobial Therapies groups at IBEC, we will encapsulate diverse antimalarial, antileishmanial, and antibiotic drugs (both in current use and newly discovered in our laboratories) in different types of nanocarriers, such as liposomes and several types of new polymers. For their targeting to parasite and bacterial cells, these nanovectors can be eventually functionalized with ligands against microbial antigens. Such ligands

will preferentially be DNA aptamers developed ad hoc against either whole parasite cells or specific known protein markers of the pathogens. At the end of the project we aim to develop a new technology to deliver efficiently antimalarial, antileishmanial and antimicrobial drugs.

Selected publications from the last 2 years:

Blanco-Cabra et al (2021) NPJ Biofilms Microbiomes 7:62.
Cendra and Torrents: (2020) Virulence 11:862; (2021) Biotechnol Adv 46:107734.
Moya-Andérico et al (2021) Chemosphere 266:129235.
Lantero et al (2020) J Biomed Nanotechnol 16:315.
Avalos-Padilla et al (2021) PLoS Pathog 17:e1009455.
Biosca et al (2020): J Control Release 331:364; Antimicrob Agents Chemother 64:e02135-19.

 

Job position description

We will look for an enthusiastic, organized, and autonomous Ph.D. candidate with a degree in Biotechnology, Biochemistry, Biology, or similar areas. English proficiency and laboratory experience acquired during a Master Thesis will be also required. During year 1, the fellow will be trained by the team in the techniques that will be used during the study, especially the in vitro culture of pathogenic bacteria (P. aeruginosa, S. aureus and others), Plasmodium falciparum, and Leishmania infantum parasites, and the techniques for drug encapsulation and their targeted delivery. During year 2, the fellow will develop DNA aptamers against the selected parasite cells and/or recombinant proteins from the pathogens and will explore their capacity to block their growth in in vitro cultures. During year 3, in vivo assays in mice will be performed, together with completion of all analyses, statistics, interpretation of results, and writing of the Ph.D. Thesis. Scientific articles will be submitted to Q1 open access journals (e.g. PLOS Pathogens, Journal of Controlled Release, Nature Communications, mBio). The results will be presented at international congresses (e.g. CLINAM, Pan-African Malaria Conference, European Congress of Clinical Microbiology and Infectious Diseases). One three- to six-month stay will be done at some selected national or international laboratory to complete the experimental work and expose the student to the dynamics of scientific collaborations while expanding her/his skills in new techniques not available at IBEC. During the 3 years of the fellowship, the Ph.D. fellow will acquire a strong knowledge of the cellular biology and physiopathology of P. falciparum, L. infantum and bacterial pathogens; s/he will gain this knowledge through lab work, regular meetings with the Ph.D. co-supervisors, bi-weekly journal clubs and weekly group meetings, and through daily readings of literature related to the field.

The Ph.D. fellow will also benefit from the research and clinical environment of the Barcelona Institute for Global Health (ISGlobal), where one of the supervisors of this Ph.D. proposal is co-affiliated. ISGlobal hosts groups working on a wide spectrum of infectious diseases, at both basic and applied levels, which is a deeply enriching scenario for the professional training of our students.