- Type de poste: PhD/Doctorat
- Secteur : Public
- Localité : International
- Limite de candidature : 15/06/2022
- Profil de poste:
Recherche et innovation
- Domaine(s) :
Microbiologie et Immunologie, Autre
Staphylococcus aureus is among the leading causes of nosocomial and community acquired infections due to the fast acquisition of antibiotic resistance. In nature, main factors contributing to the S. aureus population control are bacteriophages. Those, that are obligatorily lytic, can kill infected S. aureus cells. They are considered to be alternatives to antibiotics in the treatment of infections by antibiotic-resistant S. aureus strains.
The majority of therapeutic staphylococcal phages belong to the Kayvirus genus of Twortvirinae subfamily of Caudovirales. They have large genomes (127- 149 kb), can encode about 200 proteins, are able to lyse the majority of strains in clinical S. aureus strain collections and can destruct staphylococcal biofilms.
Despite the great interest in these phages the functions of only less than half of their genes are known. It is also unclear what are the mechanisms underlying differences in strain specificity of particular kayviruses including the ability to overcome the restriction-modification systems of certain hosts.
Elucidation of these mechanisms is crucial for the progress in the construction of genetically modified kayviruses of desired host specificity and for the development of anti-staphylococcal phage therapies. Results of initial studies suggest that differences in the strain specificity of particular kayviruses may be correlated with the presence/absence of certain accessory genes in their genomes.
The aim of this project is to functionally analyse accessory and potential antirestriction genes of an especially wide strain-range kayvirus using the reverse genetic approach.
Genes for studies have been selected based on comparative analysis of various kayviruses genomes and specificity, and on in silico preliminary analysis of predicted kayviral proteins.
Their functions will be studied by the phenotypic analysis of phage mutants depleted of these genes and constructed in the project as well as by the phenotypic analysis of S. aureus cells carrying the selected genes cloned in a plasmid.
The contribution of particular genes to the kayvirus strain specificity determination and to the kayvirus therapeutic efficacy will be studied with the use of diversified S. aureus strain collection.
Comparative genomic analysis of pairs of related S. aureus strains representing isolates sensitive and resistant to particular kayviruses will be used to identify S. aureus determinants of susceptibility to these phages. Methodology will include basic microbiological and molecular biology techniques, gene cloning and expression, genomic, transcriptomic and proteomic analysis, site-directed mutagenesis, CRISPR-Cas-mediated selection of desired mutants, comparative genomic studies.
The studies will be financed from the National Science Centre OPUS project entitled “Functional genomic analysis of Staphylococcus aureus Kayvirus genus phages in a search for molecular basis of wide host-range and the strategies of survival with a host population”. A part of studies will be implemented in collaboration with foreign laboratories.
Required Research Experiences
Requirements for the candidate:
a) hold a degree of Master of Science [Magister], Master of Engineering [Magister Inżynier], medical doctor or equivalent in the field of: exact sciences, natural sciences, medical sciences or related disciplines, granted by a Polish or foreign university; a person who does not possess the qualifications described above may take part in the competition, but must obtain the qualifications in question and provide the relevant documents before the start of the programme at the Doctoral School (i.e., October 1, 2022);
a) an application for admission to the Doctoral School, together with consent to the processing of personal data for the recruitment procedure and a statement on familiarising oneself with recruitment rules and conditions (link to the form)
b) a copy of the diploma from a university or the candidate’s statement on the estimated graduation date;
c) a scientific curriculum vitae including information on the candidate’s participation in scientific projects and other related
activities, such as publications, involvement in science club, participation in academic conferences with an oral or poster
presentation, national and international internships, prizes and awards, participation in grants, popularization of science, voluntary work;
d) a list of completed university courses with marks;
e) a motivation letter;
f) contact details to at least one academic adviser or academic staff member holding at least a doctor’s degree, who has agreed to give an opinion on the applicant. The opinion should not be attached to the application;
g) in the case of having a disability certificate or a certificate on the degree of disability, or a certificate referred to in Article 5 and Article 62 of the Act of 27 August 1997 on Vocational and Social Rehabilitation and Employment of Persons with Disabilities ‒ a statement of holding such certificate;
h) candidates holding a diploma of completing studies abroad shall additionally attach a certified translation of the diploma, including the supplement, into Polish or English, unless the diploma or an official copy thereof, including the supplement, has been issued in English.
Language of documents: either English or Polish up to the candidate’s choice