BEMÆRK: Ansøgningsfristen er overskredet
Two PhD fellowships in protein design and evolution
PhD Projects in design and evolution of functional D/L-micropeoteins
Department of Chemistry
Faculty of SCIENCE
University of Copenhagen
Department of Chemistry, Chemical Biology section invites applicants for a PhD fellowship in design, synthesis and evolution of biofunctional microproteins, particularly enzymes and recognition molecules. The project is part of the research project synthetic D/L-microproteins , which is financed by Villum Foundation and NNF.
Start date is expected to be 1 October 2023 or as soon as possible.
The project
At least two projects are planned, both of which involve use of molecular modelling, particularly mutational MD- calculations which include a virtual screen for the most stable folds in de novo design of proteins composed of natural as well as unnatural both L- and D-amino acids.
In one project, the designs will be directed towards synthesis of active artificial proteases and the activity will be investigated in combinatorial substrate libraries. The best results from initial experiments involving design based on structure of typical Cys-, Asp-, Ser-, and metalloproteases will be selected and utilized in optimization studies. Activity will investigated in detail including kinetics and upon complete purification the structure of the protein wil be determined by crystallography or NMR spectroscopy to understand structure activity relationship. Active proteases will be further evolved towards pathogenic proteins such as Alzheimer Ab-1-42 or endogenous proteins such as cancer associated XIAP, an inhibitor of apoptosis. FRET-substrates from the target proteins will be produced and the active site of the active protease will subjected to combinatorial variation to evolve the activity and selectvity towards the pathogen.
In the second PhD study synthetic D/L-microproteins for molecular recognition will be designed by mutational MD and synthesized using automated peptide sythesis. For this project known very high affinity monoclonal antibodies, e.g. Humira against inflammation, will act as one model for which the crystal structure is known. The structure 3WD5 of the interacting part of the antibody will constitute a starting point for the design and a stable fold with a hydrophobic core, polar periphery and recognition residues will be designed and screened for TNF-alfa interaction and subjected to combinatorial evolution. A second model will be sialyl LewisA antigen also known as thew pancreatic cancer marker CA19-9. Here the antigen will be purchased and immobilized on resin for screening of microprotein binding using fluorescent labelled microprotein libraries. The design will be towards the preferred known CA19-9 structure of the antigen focusing on the most important interaction with the two terminal sugars, sialic acid and fucose. Designed microproteins will be stabilized with click bridges and click handles to be used in targeting xiap-Cas7 interaction inhibitors (a b-body) and above xiap protease to pancreatic cancer cells. Throughout the project will attempt to determine structure of microprotein ligand interactions.
Who are we looking for?
We are looking for candidates with a broad experience within the fields of molecular modelling, peptide synthesis, NMR or protein crystallography, enzyme / protein screening and analysis. Applicants can have a background from crystallography or NMR spectroscopy, combined with molecular modelling, peptide synthesis, enzymology, and knowledge in protein expression will also be appreciated. Generally a background in chemical biology with a focus on chemical synthesis and chemical design is of interest.
Our group and research- and what do we offer?
Center of evolutional chemical biology has a unique platform for combinatorial evolution of chemical properties and this platform will be used in the above projects. It constitutes virtual as well as real molecular library screening technologies. We use MOE for mutational MD-evolution of proteins in a design process and design microproteins that are accessible by synthesis. We have Gyros unique automated synthesis machines and can easily assemble 50-60 mer microproteins composed of any combination of natural and unnatural amino acids. This allow us access to unprecedented protein diversity even in such short sequences. We have ICR MS, Bruker microflex, and Xevo QTOF-UPLC in the laboratory, 500 MHz NMR and access to 800 MHz at DTU. We have a prep HPLC, FPLC, fluorescense microscopes, beadsorter, optical bead decoder, bioforte red96 binding kinetics, GMO cell laboratory, in our laboratories and access to many types instruments in Department of Chemistry. We have several shared high end computers for interactive modelling studies. The group is currently 9 members including our excellent undergraduate students.
The group is a part of Department of Chemistry, Faculty of SCIENCE, University of Copenhagen. We are located in Copenhagen.
We offer creative and stimulating working conditions in dynamic and international research environment. Our research facilities include modern laboratories and high end infrastructure and equipment required for performance of the planned research.
Principal supervisor is Professor & Nobel Laurate Morten Meldal, Department of Chemistry, UCPH, Email-PA: Benedicte Nyvang Vævest brk@chem.ku.dk, Direct: meldal@chem.ku.dk, Mob. +45 21308299
The PhD programme
With a Master degree, you can undertake the PhD programme as:
A three year full-time study within the framework of the regular PhD programme (5+3 scheme), only if you already have an education equivalent to a relevant Danish master’s degree.
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Qualifications needed for the regular programme
To be eligible for the regular PhD programme, you must have completed a degree programme, equivalent to a Danish master’s degree (180 ECTS/3 FTE BSc + 120 ECTS/2 FTE MSc) related to the subject area of the project, e.g. a chemistry, biochemistry or medicinal chemistry education with focus on organic and peptide synthesis, protein chemistry, modelling/theoretical cemistry. For information of eligibility of completed programmes, see General assessments for specific countries and Assessment database.
Terms of employment in the regular programme
Employment as PhD fellow is full time and for maximum 3 years.
Employment is conditional upon your successful enrolment as a PhD student at the PhD School at the Faculty of SCIENCE, University of Copenhagen. This requires submission and acceptance of an application for the specific project formulated by the applicant.
Terms of appointment and payment accord to the agreement between the Danish Ministry of Taxation and The Danish Confederation of Professional Associations on Academics in the State. The position is covered by the Protocol on Job Structure.
Responsibilities and tasks in the PhD Programe
- Carry through an independent research project under supervision
- Complete PhD courses corresponding to approx. 30 ECTS / ½ FTE
- Participate in active research environments, including a stay at another research institution, preferably abroad
- Teaching and knowledge dissemination activities
- Write scientific papers aimed at high-impact journals
- Write and defend a PhD thesis on the basis of your project
- Professional qualifications relevant to the PhD project as outlined above
- Relevant publications
- Relevant work experience
- Other relevant professional activities
- Curious mind-set with a strong interest in molecular properties, recognition and transformation
- Good language skills particularly in english, including publication writing skills
Application and Assessment Procedure
Your application including all attachments must be in English and submitted electronically by clicking APPLY NOW below.
Please include:
- Motivated letter of application (max. one page)
- Your motivation for applying for the specific PhD project/State which PhD project you are applying for.
- Curriculum vitae including information about your education, experience, language skills and other skills relevant for the position
- Original diplomas for Bachelor of Science or Master of Science and transcript of records in the original language, including an authorized English translation if issued in another language than English or Danish. If not completed, a certified/signed copy of a recent transcript of records or a written statement from the institution or supervisor is accepted.
- Publication list (if possible)
- Reference letters (if available)
We reserve the right not to consider material received after the deadline, and not to consider applications that do not live up to the above mentioned requirements.
The further process
After deadline, a number of applicants will be selected for academic assessment by an unbiased expert assessor. You are notified, whether you will be passed for assessment.
The assessor will assess the qualifications and experience of the shortlisted applicants with respect to the above mentioned research area, techniques, skills and other requirements. The assessor will conclude whether each applicant is qualified. The assessed applicants will have the opportunity to comment on their assessment. You can read about the recruitment process at http://employment.ku.dk/faculty/recruitment-process/.
Interviews with selected candidates are expected to be held by zoom in the week 3/7-7/7 2023. Apropriate zoom invitations will be issued by the interview committee.
Questions
For specific information about the PhD fellowship, please contact the principal supervisor through brk@chem.ku.dk
General information about PhD study at the Faculty of SCIENCE is available at the PhD School’s website: https://www.science.ku.dk/phd/.
The University of Copenhagen wishes to reflect the surrounding community and invites all regardless of personal background to apply for the position.
INFORMATIONER OM STILLINGEN:
- Arbejdspladsen ligger i:
Gladsaxe Kommune
-Virksomheden tilbyder:
-Arbejdsgiver:
KU - SCIENCE - NBI, H.C. Ørsted Instituttet, Universitetsparken 5, 2100 København Ø
-Ansøgning:
Ansøgningsfrist: 14-06-2023; - ansøgningsfristen er overskredet
Ved skriftlig henvendelse: https://candidate.hr-manager.net/ApplicationInit.aspx?cid=1307&ProjectId=159408&DepartmentId=18975&MediaId=4632&SkipAdvertisement=true
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