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Kontakt:
Maksymilian Szymczak

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Role of glycans in neurotransmitter receptor mechanics (Supervisor: dr Mateusz (Matt) Sikora)

Role of glycans in neurotransmitter receptor mechanics (Supervisor: dr Mateusz (Matt) Sikora)

Project description:

Neurotransmitter receptors (NTRs) mediate synaptic transmission and are key proteins of the nervous system. Like most neuronal membrane proteins, these receptors are heavily glycosylated, i.e., modified by the covalent addition of complex sugars, glycans. In the mammalian brain, NTRs display atypical glycans that are usually not found on surface-expressed proteins in other cell types.  The role of these atypical glycans in signal transduction and receptor dynamics is not yet understood, hindering the development of new therapeutic factors.

Our ongoing work suggests that glycans affect available NTR conformation, hinder interactions with specific pharmacological agents and modulate NTR diffusion at the neuronal surface, likely affecting receptor mechanics at multiple levels. 

Within this project, you will work at the interface between computational biology, biophysics, and neurobiology to characterize the role of glycans in NTR dynamics and function. In close collaboration with experts in neuron cell biology, you will apply multi-scale physics-based computer simulations and develop new techniques to provide a better biophysical understanding of single-molecule tracking and electrophysiological experiments reporting on NTR activity and dynamics in distinct glycan backgrounds. As an active agent within 3 non-exclusive projects, you will:

  1. Apply computer simulations to combine available cryo-EM datasets with glycoproteomics data to generate more realistic and fully glycosylated atomic models of GABA and AMPA, main inhibitory and excitatory receptors, and/or
  2. Perform single-receptor computational electrophysiology and ligand binding simulations to determine how glycans regulate GABA and AMPA receptor activation and ion conduction, and/or
  3. Simulate large patches of the neuronal membrane of various compositions to elucidate the role of glycans in receptor dynamics.

The perfect Candidate should have: 

  • MSc or equivalent degree in physics, chemistry, biophysics, computer science or similar
  • Interest in physics of biological systems 
  • Previous experience in programming/scripting (Python, bash, etc.), biomolecular simulations engines (GROMACS, NAMD, Charmm) are not required but are a plus. 
  • Excellent communication skills and strong working proficiency in English. 

Starting date: 1st of May 2023 

How to apply?

In case of further questions about the project, do not hesitate to contact Mateusz (Matt) Sikora directly.
Please send your application documents to the following e-mail addresses: biomedical.phd@uj.edu.pl and to the Project Manager dr Mateusz (Matt) Sikora masikora@biophys.mpg.de

Schedule of the competition:

  • Opening of the competition: 04.11.2022
  • Application submission deadline: 08.11.2022, noon CET
  • Entrance exams: 24.11-25.11.2022
  • Committee meeting - no later than: 25.11.2022
  • Exam results: 28.11.2022
  • Entries to the Doctoral School: 29.11-01.12.2022
  • Entries to the Doctoral School - reserve list: 02.12.2022

The environment:

You will join the Dioscuri Centre for Modelling of Post-translational Modifications led by Mateusz (Matt) Sikora. Dr Sikora is an expert in computer simulations of biological systems with particular focus on glycosylation and other modifications of proteins. The Malopolska Centre of Biotechnology is a world-renowned research institute offering a supportive and interdisciplinary research environment at the international level. We offer very good financial conditions and a cooperative working environment with access to cutting-edge computing facilities. By joining the Centre, you will have an opportunity to be involved in joint scientific and networking activities together with the Theoretical Biophysics dept. at the Max Planck Institute of Biophysics in Frankfurt, Germany, led by prof. Gerhard Hummer, partner of the Centre. 

The Malopolska Centre of Biotechnology and the Dioscuri Centre strive to ensure a workplace with equal opportunities. We celebrate diversity and are committed to creating an inclusive environment for all members irrespective of gender, nationality or disabilities.

Detailed terms and procedures of admission.

Documents required at the recruitment application stage:

  • a curriculum vitae (CV) with particular emphasis on scientific achievements;
  • a motivation letter, explaining how the applicant’s background and research interests make them a suitable candidate for the position;
  • the names of the researchers giving references to the candidate (their contact number and academic title);
  • documents demonstrating the scientific achievements listed in the curriculum vitae, e.g. first page of the article;
  • transcript of grades: diploma supplement or the official transcript of grades, or another document listing completed courses and grades. Information about the grading scale must be
  • included.

In the event of the persons referred to in Article 186, section 2 of the Act, two opinions confirming the high quality of their research work and the high level of advancement of such work, issued by: a research fellow holding at least the academic degree of doctor habilitated or being an employee of a foreign higher education institution or a research institution, that has significant achievements in academic issues related to the curriculum.

Any document submitted in a language other than Polish or English must be accompanied by a certified translation into Polish or English.

Documents required for enrollment:

  • the original application and a photograph;
  • a photocopy and the original for inspection:
  • a. a diploma certifying the holding of a degree of Master, Master Engineer or equivalent in a field of study from among those indicated in the detailed conditions of recruitment, or
  • b. a diploma of completion of studies abroad, giving the right to enrol in a course of doctoral  studies in the issuing country or recognised as equivalent to the appropriate Polish diploma confirming the qualifications of the second degree;
  • if the candidate has not yet been issued such a diploma by the deadline for admission,
  • he/she shall submit a certificate of completion of such studies and a written undertaking to provide the diploma of higher education entitling to enrol in a course of doctoral studies within the prescribed deadline;
  • for inspection: identity document (passport in case of foreigners);
  • originals of all other documents provided at the registration stage in the form of a scan.
  • In the event of exposure to harmful, noxious or hazardous factors, the applicant will, at the time of registration, be referred for a medical examination by an occupational medicine physician. The candidate shall be obliged to deliver, within the time limit set by the programme manager, a medical certificate confirming the absence of contraindications to take up education.

Higher education diplomas awarded abroad should:

  • bear an apostille clause if the issuing country is covered by the Convention abolishing the requirement legalisation for foreign public documents, done at The Hague on 5 October 1961 (Journal of Laws of 2005, No. 112, item 938) or
  • be subjected to legalisation, in other cases.

Any document submitted in a language other than Polish or English must be accompanied by a certified translation into Polish or English.

Insurance:

Each doctoral student, including a foreigner, admitted to the doctoral school is obligatorily subject to health insurance if he/she is not covered by such insurance on other grounds (e.g. employment relationship, contract of mandate, business activity, insured as a family member under 26 years of age, as the spouse of an insured person). The health insurance contribution is paid by Jagiellonian University and is financed from the State budget. In addition, a doctoral student receiving a doctoral scholarship is subject to compulsory retirement and disability insurance and accident insurance.

IMPORTANT:

A person admitted to the doctoral school begins education and acquires doctoral student rights upon taking the oath. The Department of Personal Affairs reports each doctoral student admitted to the School to compulsory health and social insurance at the commencement of education, i.e. from 1 October at the earliest. Until that time foreign candidates are obliged to cover the costs of insurance for the time of travel, treatment, etc. individually.

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