Procedure no. DSMBBC/2024/IMol/8 “Dynamic RNA:RNA interactions at the catalytic center of the spliceosome”

Job title:

Procedure no. DSMBBC/2024/IMol/8 “Dynamic RNA:RNA interactions at the catalytic center of the spliceosome”

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Job description

Offer DescriptionThe long-term interest of my group is focused on how RNA:RNA interactions within the spliceosome determine the catalytic function of this complex ribonucleoprotein enzyme. The proposed project will investigate changes within the RNA catalytic core of the spliceosome associated with the progression of the splicing reaction through its two-step catalysis. We will start by investigating if the spliceosomal catalytic triplex, which plays a critical role in splicing catalysis. We suggest that this triple-stranded element changes its conformation at different stages of catalysis in a way similar to what was described in group II intron ribozymes by structural biology methods. Strikingly, however, cryo-EM structures of the spliceosome do not detect any such changes. We will carry out our analysis relying on yeast genetics, which allows us to perform high-precision molecular enzymology tests on living yeast cells. Subsequently, we will expand our analysis to other changes expected to occur within the catalytic center between the two catalytic reactions of splicing.Many combinations of U2 and U6 mutant alleles within the catalytic center are inviable. To gain access to study the underlying causes of this inviability, we will rely on the U2-BS orthogonal system (Smith et al., 2009), in which appropriately altered U2 sequences can interact with the corresponding tailor-made orthogonal reporter introns. In this system, the splicing of endogenous introns is not affected by orthogonal U2 mutants, allowing for in vivo analyses typically not accessible to genetic methods. Future plans include the expansion of the orthogonal system to U6-5’SS interactions. Although this part of the project is considered risky, the potential gains are very significant.Together, the anticipated results will provide new insights into the basic mechanisms of splicing. In particular, these studies will shed light on still poorly understood mechanisms of the second step of splicing. Because of the high level of conservation of splicing mechanisms, the anticipated results will also apply to splicing mechanisms in humans.Where to apply WebsiteRequirementsResearch Field Biological sciences Education Level Master Degree or equivalentSkills/QualificationsHold 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., March 1, 2025). Education at the Doctoral School begins on March 1 2025;Specific RequirementsThe candidate must be fluent in English (written and spoken), and be interested in mechanistic studies at the molecular level. Previous experimental training in the yeast system or work with RNA is strongly preferred, though not necessary. We look for candidates with a strong motivation for experimental work: planning and executing experiments. Creativity, analytical thinking, and the ability to work both independently and as a part of a team will be highly valued.Languages ENGLISH Level ExcellentResearch Field Biological sciencesAdditional InformationSelection processThe recruitment process consists of two stages:a) selection of candidates by the Committee based on their previous achievements and academic performance presented in the documents submitted; for each position no more than 5 applicants who have achieved the highest scores, but no less than 60% of the maximum points, shall be qualified for the next stage;b) an interview conducted by the Committee including in particular:

• a presentation delivered by the candidate containing the outcomes of his/her research (a Master’s thesis or other research work carried out by the candidate); the presentation must not last longer than 10 minutes;
• questions asked by the members of the Committee related to the presented project, the methods used and interpretation of the results obtained;
• questions asked by the members of the Committee related to the proposed PhD programme described in the recruitment announcement;
• questions related to the candidate’s motivation for scientific work.

Stage One

• learning outcomes (a scale of the evaluation: 0.0 – 6.0 points);
• participation in a scientific project or an academic conference (a poster or oral presentation) (a scale of the evaluation: 0.0 – 1.0 points);
• co-authorship of a research paper (depending on the role in the publication) (a scale of the evaluation: 0.0 – 1.0 points);
• involvement in science club (a scale of the evaluation: 0.0 or 0.5 points);
• other achievements, e.g., awards, honors, scholarships, domestic and foreign internships, voluntary work, popularization of science (a scale of the evaluation: 0.0 – 1.5 points).

Stage Two

• understanding of the project performed and methods used; the ability to interpret the results obtained; knowledge in the field related to the presented project (a scale of the evaluation: 0-10 points);
• knowledge in the field related to the proposed PhD programme described in the recruitment announcement (a scale of the evaluation: 0-10 points);
• form of presentation of the candidate’s results (a scale of the evaluation: 0-3 points).

Website for additional job detailsWork Location(s)Number of offers available 1 Company/Institute Institute of Biochemistry and Biophysics Polish Academy of Sciences Country Poland City Warsaw Postal Code 02-106 Street ul. Pawińskiego 5aContact CityWarsaw WebsiteStreetul. Pawińskiego 5a Postal Code02-106 E-MailPhDschool-recruitment@ibb.waw.plSTATUS: EXPIREDShare this page

Expected salary

Location

Warszawa, mazowieckie

Job date

Wed, 08 Jan 2025 23:28:21 GMT

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