Program no. DSMBBC/2024/7 The role of RNF2 in the regulation and function of human DNA polymerase iota

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Program no. DSMBBC/2024/7 The role of RNF2 in the regulation and function of human DNA polymerase iota

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Job description

Offer DescriptionGenome integrity maintenance is fundamental for all living organisms. Cells are equipped with an array of DNA mechanisms ensuring prompt and faithful duplication of information encrypted in DNA. Still, DNA is prone to lesions induced by endogenous and exogenous sources. Although damaged DNA is rapidly targeted to repair, some of the lesions escape it and pose a threat, which is particularly dangerous to actively dividing cells. Lesions may block DNA replication, hampering thus cell division which may cause cell death. As an alternative, cells can temporarily tolerate the damage in DNA which permits to completion of the DNA duplication. In one of the DNA damage tolerance mechanisms, a special type of DNA polymerases is employed to traverse the damage in a process named translesion synthesis (TLS). However, while permitting cell survival after DNA damage, their activity is often mutagenic and needs to be strictly controlled. A TLS regulation is a multi-level process and depends largely on posttranslational modifications of engaged proteins and interactions between the proteins involved. Polymerase iota is the most mutagenic human DNA polymerase, but its cellular role remains elusive. The necessity of tight governing of polymerase iota is underlined by the fact that both, lack and overproduction of polymerase iota have been correlated with tumorigenesis. Posttranslational modifications and protein-protein interactions play a fundamental role in the regulation of polymerase iota. It has been shown by others and by our research that polymerase iota can be a substrate of mono- and polyubiquitination. Recently we identified RNF2, an E3 ubiquitin ligase, as a new interacting partner of polymerase iota. Interestingly, RNF2 does not seem to directly ubiquitinate polymerase iota, however, independently of the interaction, plays a role in the maintenance of polymerase iota’s cellular level. This indicates that the relationship between RNF2 and polymerase iota is on more than one level. The process requiring polymerase iota-RNF2 association, as well as identification of the the role of RNF2 in the regulation of the level of polymerase iota protein will be of our future investigation.The proposed research will be conducted in human healthy and cancerous cell lines and extracellular systems. We will utilize a range of biochemical, microscopic, molecular biology, and bioinformatic techniques.We expect that the proposed approach will, on one hand, help to identify new mechanisms of polymerase iota regulation, and will help to determine a cellular role played by this enzyme. Understanding the functioning and control of TLS proteins is not only cognitive. Due to their ability to synthesize the damaged DNA template, these proteins can counteract anti-cancer treatments that are largely based on inducing DNA lesions in intensively dividing cells. Therefore, we believe that in the future, the obtained results will provide helpful inputs in designing innovative, personalized anti-cancer therapies.RequirementsResearch Field Biological sciences Education Level Master Degree or equivalentSkills/Qualifications

• 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., 1st October 2024) Education at the Doctoral School begins on 1st October 2024;

Excellent written and verbal communication skills in English. Passion for science and strong motivation for research work. Hands-on experience in molecular/cellular biology, tissue culture, and microscopy techniques will be an added advantage.Languages ENGLISH Level ExcellentResearch Field Biological sciencesAdditional InformationBenefits

• Scholarship amount (net, monthly, PLN): 1st year: 4000; 2nd year: 4000; 3rd year: 4 739,51; 4th year: 4 739,51;

Surcharge for the multi sport card, parking, optional language courses.Selection processThe recruitment process consists of two stages: * 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;

• 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 5aWhere to apply WebsiteContact CityWarsaw WebsiteStreetul. Pawińskiego 5a Postal Code02-106 E-MailPhDschool-recruitment@ibb.waw.plSTATUS: EXPIRED

Expected salary

Location

Warszawa, mazowieckie

Job date

Wed, 08 May 2024 04:05:44 GMT

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