Program no. DSMBBC/2024/8 Mechanisms of human protein kinase CK2 activity regulation

Job title:

Program no. DSMBBC/2024/8 Mechanisms of human protein kinase CK2 activity regulation

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Job description

Offer DescriptionThe proposed programme aims to elucidate the role of CMGC-insert in the recognition and activity regulation of protein kinase CK2 substrate. Kinase CK2 is a member of the CMGC group of eukaryotic protein kinases that are involved in many essential processes but have also been implicated in various dreadful diseases. There is an undeniable necessity for developing new, more specific inhibitors that can be used to inhibit these kinases. However, understanding the mechanism of substrate recognition and activity regulation seems necessary to achieve this goal. CMGC-insert is a fragment highly conserved in all kinases from the CMGC group, but its function in CK2 remains to be determined. Our recent studies imply that the binding of low-mass ligands in the ATP-binding site may also affect CMGC-insert. Two main questions will be addressed:

• Is there a link between hCK2 CMGC-insert and the substrate specificity?
• Is there a direct or indirect coupling between the ATP-binding site and the CMGC insert?

A PhD student will design and obtain mutant proteins with modified CMGC-insert to answer these questions. The pull-down method with WT and mutant proteins will be used to select protein substrates. That will be how to find the substrates or other proteins that interact with the kinase through CMGC-insert. Mutants will be compared with WT regarding selected protein substrate binding affinity with Microscale Thermophoresis (MST) and Isothermal Titration Calorimetry (ITC). When required, indirect methods like Differential Scanning Fluorimetry (DSF) or Differential Scanning Calorimetry (DSC) might be used. These experiments will also be supplemented with kinetic parameters determined for both ATP and selected protein substrates. For verification of substrate binding is associated with the CMGC-insert or alters its dynamics, several different approaches may be applied: Nuclear Magnetic Resonance (NMR) spectroscopy, Fluorescence spectroscopy or Hydrogen/deuterium exchange (HDX) mass spectrometry (MS).To verify a link between the ATP-binding site and CMGC-insert, low-mass compounds that bind at the ATP-binding site will be used, and the same methods (NMR, Fluorescence and MS) will be applied. Next, the formation of the ternary complexes using at least one of three methods – DSF, MST, or ITC will be studied – to test the cross-dependency of both substrate bindings. The outcome of this work will be the description of the novel mechanism underlying substrate specificity and regulation of the activity of the CK2 through CMGC-insert. Such an approach will extend our knowledge about this fragment and state the starting point for designing new inhibitors interacting directly with CMGC-insert.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;

Required basic knowledge about expression and purification of proteins and biophysical methods.Languages ENGLISH Level GoodResearch Field Biological sciencesChemistryAdditional 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.Eligibility criteriaSelection 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 01:24:44 GMT

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