Oferty pracy w projektach finansowanych przez NCN

Nazwa jednostki: WBBiB, UJ – Kraków, Inne oferty z tego miasta »
Nazwa stanowiska: Adiunkt Badawczy
Wymagania:

- PhD in the fields of biological, chemical sciences or similar fields;
- experience in solving crystal structure employing X-ray crystallography documented by publications;
- experience in laboratory techniques such as expression of recombinant proteins, purification of proteins employing different chromatography techniques such as affinity, size-exclusion and ion-exchange chromatography;
- experience in cryo-EM or willingness to learn cryo-EM; - good knowledge of English: spoken and written;
- obtaining a doctoral degree not earlier than seven years before the year of employment in the project;
- obtaining a doctoral degree in an entity other than the entity in which employment in this position is planned, or completion of at least a 10-month continuous and documented post-doctoral internship in an entity other than the entity implementing the project and, in a country, other than the country of obtaining the doctoral degree;
- no previous cooperation with the project principal investigator in the realization of a research project financed by means of a competition.

Opis zadań:

Hydrolysis of peptide bond by proteases, is irreversible, so it must be tightly controlled to prevent damage to the cell or whole organism. One way of controlling proteolytic activity, especially in multicellular organisms, is synthesis of proteinaceous protease inhibitors. Almost all inhibitors are specific for particular proteases that share similar substrate specificity and interact directly with the active site cleft, blocking access to it for all substrates. In stark contrast, members of the α2-macroglobulin (A2M) inhibitor family inhibit a broad spectrum of proteases without disturbing their active sites. The inhibition is achieved by irreversible trap mechanisms resulting from large conformational rearrangements upon a prey protease's cleavage in the bait region resulting in encaging of the protease. The mechanism of action of A2Ms could be compared to carnivorous plants such as sundew and Venus flytrap hunting on insects. In stark contrast to these plants, trapped proteases are intact and active against small substrates. Outside metazoans, putative A2M genes are generally absent from archaea, protozoa, fungi and plants. Strikingly, they are found in Gram-negative bacteria colonising mammals but not in free-living environmental microorganisms. In this context, it is fascinating that two bacterial species express A2Ms: Porphyromonas gingivalis and Tannerella forsythia, which are major etiologic factors of periodontal diseases, affecting in its severe forms even 15% of adults worldwide. If untreated, the condition leads to the destruction of teeth supporting tissues resulting finally in tooth loss and contributes to the development and/or progression of systemic diseases such as diabetes, atherosclerosis, rheumatoid arthritis, and neurodegenerative diseases. Therefore, the main aim of the proposed project is not only a detailed biochemical and structural description of the inhibitory mechanism of periodontal A2Ms, but also their role in periodontopathogens virulence.
Key responsibilities:
1) preparation of expression constructs encoding a2-macroglobulins (A2Ms) mutants, especially ones for structural analysis;
2) solving of the three-dimensional structure of A2Ms employing X-ray crystallography and cryogenic electron microscopy (cryo-EM). To be more detailed: crystallographic trials, preparation crystals for X-ray diffraction, analysis of obtained data, preparation of samples for cryo-EM, and analysis of obtained data;
3) preparation and deposition of structural data in open access online databases;
4) preparation of figures for publication and writing of manuscripts.

Typ konkursu NCN: SONATA BIS – NZ
Termin składania ofert: 20 lipca 2031, 22:00
Forma składania ofert: email
Warunki zatrudnienia:

1. A contract of employment - 100% full-time position
2. access to laboratories that meet the requirements for the implementation of research tasks
3. employment in the Department of Microbiology conducted by a world-renowned scientist in the field of biochemistry, enzymology, infectious diseases

Dodatkowe informacje:

Required documents:
1. The application,
2. CV,
3. a copy of the doctoral diploma,
4. a summary of the most important research areas and scientific achievements,
5. list of publications (including publication and number of pages),

Data dodania ogłoszenia: 2022-06-27 16:37:02