PhD Student: DSMBBC/2023/23 An atomic-resolution understanding of how a critical metalloenzyme functions and evolves
28 Dec 2023
Job Information
- Organisation/Company
Institute of Biochemistry and Biophysics Polish Academy of Sciences- Department
Laboratory of Metalloprotein Biology- Research Field
Biological sciences- Researcher Profile
First Stage Researcher (R1)- Country
Poland- Application Deadline
19 Jan 2024 - 00:00 (Europe/Warsaw)- Type of Contract
Temporary- Job Status
Full-time- Hours Per Week
40- Offer Starting Date
1 Mar 2024- Is the job funded through the EU Research Framework Programme?
Not funded by an EU programme- Is the Job related to staff position within a Research Infrastructure?
No
Offer Description
Our lab studies the structure and function of metalloproteins. It’s estimated that approximately one-third of all proteins, and nearly half of all enzymes, require an essential metal ion to function (Waldron et al., Nature 2009). Most metalloproteins are assumed to be specific for their cognate metal cofactor, showing reduced activity with other metal ions in vitro and in vivo. But the mechanisms by which metalloproteins become optimised for their target metal ion remain unknown. Furthermore, analyses of protein sequence databases demonstrate that the specificity of metalloproteins can change over evolutionary time, likely in response to changes in metal availability in the environment. For example, such changes were likely crucial in the adaptation of early organisms to the oxygenation of the atmosphere through photosynthesis, which would have dramatically altered environmental metal abundance. Our recent work has demonstrated that a more recent change in metalloenzyme specificity enabled a commensal bacterium to evolve pathogenicity by overcoming metal starvation within the host (Garcia et al., PLoS Pathog. 2017).
In this project, we will build on our recent biochemical, microbiological and evolutionary studies of the common metalloenzymes, the family of iron- or manganese-dependent superoxide dismutases (Sendra et al., Nat. Ecol. Evol. 2023). These enzymes play crucial role in cellular defence against oxidative stress and in pathogenicity (Frye et al., J. Inorg. Biochem. 2022). We will apply cutting-edge methodologies in biochemistry, biophysics and structural biology to determine how these SOD enzymes function at atomic resolution, in collaboration with world-leading technical experts. We will test hypotheses about how subtle differences within the conserved overall structure of these metalloenzymes regulate the differential reactivities of their metal cofactor to give rise to the different metal preferences that we have observed across the protein family. We will also determine how they perform their chemical reaction within a dynamic structure, including testing the role of dimerisation in catalysis. We will leverage bioinformatic analyses to study SOD sequences to determine how the differences in metal-preferences that we have observed across this enzyme family has evolved. We will identify key amino acid residues that have changed within natural SOD isozymes to give rise to these functional differences in their cofactor specificity through bioinformatic analyses, and then use mutagenesis approaches to test their hypothetical role biochemically.
The successful candidate have a strong background in either biochemistry, biophysics or bioinformatics, with a keen interest in all of these subject areas. They will obtain high-level skills in molecular biology and biochemistry, including extensive experience of recombinant protein expression and purification, the assessment of enzymatic activity and the quantification of metal-loading of metalloenzymes. Through collaborations with leaders in their respective fields, they will also gain experience and skills in structural biology and biophysics methods, as well as advanced bioinformatic approaches. High-resolution structures will be determined for the target metalloenzymes and their mutant forms, using crystallographic and magnetic resonance approaches.
Requirements
- Research Field
- Biological sciences
- Education Level
- Master Degree or equivalent
Skills/Qualifications
Holding 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, 2024). Education at the Doctoral School begins on March 1 2024
- Languages
- ENGLISH
- Level
- Good
Additional Information
Benefits
Scholarship amount (net, PLN, monthly):
1st year: 4000 (approximately); 2nd year: 4000 (approximately); 3rd year: 4500 (approximately); 4th year: 4500 (approximately)
Selection process
The 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;
(Selected candidates will be invited for the interview that will take place from 22/01/2024 to 26/01/2024 (the exact date will be given in the invitation)).
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.
Additional comments
Required documents:
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 application 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.;
- Website for additional job details
https://ibb.edu.pl/en/phd-studies/rekrutacja/
Work Location(s)
- Number of offers available
- 1
- Company/Institute
- Institute of Biochemistry and Biophysics Polish Academy of Sciences
- Country
- Poland
- State/Province
- Mazovia
- City
- Warsaw
- Postal Code
- 02-106
- Street
- ul. Pawińskiego 5a
Where to apply
- Website
https://ibb.edu.pl/en/phd-studies/rekrutacja/
Contact
- State/Province
Mazovia- City
Warsaw- Website
https://ibb.edu.pl/en/phd-studies/rekrutacja/- Street
ul. Pawińskiego 5a- Postal Code
02-106
[email protected]
STATUS: EXPIRED
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