Post-doctoral fellow in Organic Chemistry

Subject description

The subject of the position is organic chemistry at the interface with chemical biology. The research concerns the development of a modular chemical platform for targeted protein degradation in bacteria (BacPROTACs) as a new strategy against antimicrobial resistance (AMR). Bifunctional molecules are designed and synthesised to recruit endogenous bacterial proteolytic machinery, such as the ClpC:ClpP system, in order to selectively degrade essential proteins in drug-resistant Staphylococcus aureus , rather than inhibiting them.

The work spans the full cycle from molecular design and multistep synthesis of degrader molecules — combining target-binding ligands, tunable linkers and protease-recruiting motifs — to the biochemical and microbiological evaluation of these molecules. The holder of the position is therefore expected to work actively on both sides of this interface, and in particular to take part in the development, validation and implementation of assays for protein degradation and antibacterial activity. The project is carried out in close collaboration with an infection biology group at Lund University, which provides established infection-relevant bacterial models and omics workflows.

Work duties

The main duties involved in a post-doctoral posistion is to conduct research. Teaching may also be included, but up to no more than 20% of working hours. The position shall include the opportunity for three weeks of training in higher education teaching and learning.

Detailed description of the work duties

• Design and multistep synthesis of bifunctional degrader molecules (BacPROTACs), including ligands, linkers and protease-recruiting elements.
• Development, validation and routine application of biochemical assays for target engagement and protein degradation, including work with recombinant bacterial proteins.
• Evaluation of compounds for antibacterial activity in S. aureus , including infection-relevant bacterial states, in collaboration with the partner laboratory.
• Extensive compound characterisation and purity assessment using NMR, LC-MS, HRMS, IR and chromatographic methods.
• Interpretation and documentation of structure–activity and structure–degradation relationships to guide the next round of molecular design.
• Supervision of thesis students and doctoral candidates.
• Collaboration with industry and wider society.
• Participation in group and project meetings and seminars.
• Administration related to the work duties listed above.

Qualification requirements

Appointment to a post-doctoral position requires that the applicant has a PhD, or an international degree deemed equivalent to a PhD, within the subject of the position, completed no more than three years before the date of employment decision. Under special circumstances, the doctoral degree can have been completed earlier.

Additional requirements

• Very good oral and written proficiency in English.
• Documented experience of multistep organic synthesis, including purification and structural characterisation of small molecules.
• Documented experience of experimental work at the interface between chemistry and biology, such as biochemical, enzymatic, cell-based or microbiological assays.
• Ability to work independently and in a structured and reliable manner, and to document and report experimental work accurately.

Assessment

Assessment criteria and other qualifications

This is a career development position primarily focused on research. The position is intended as an initial step in a career, and the assessment of the applicants will primarily be based on their research qualifications and potential as researchers.

Particular emphasis will be placed on research skills within the subject.

For appointments to a post-doctoral position, the following shall form the assessment criteria:

• A good ability to develop and conduct high quality research.
• Teaching skills.

Additional assessment criteria

• The ability to combine synthetic organic chemistry with chemical biology within a single project is a strong merit, and is the central qualification sought for this position.
• Experience of assay development, including establishing, troubleshooting and validating new biochemical or cell-based assays, is a strong merit.
• Experience of bifunctional molecules such as PROTACs, molecular glues or other targeted protein degraders is a strong merit.
• Experience of recombinant protein expression, purification and handling is a merit.
• Experience of microbiology and antibacterial susceptibility testing, such as MIC determination, time-kill analyses or biofilm assays, is a merit.
• Experience of proteomics, chemoproteomics or transcriptomics workflows is a merit.
• Experience of medicinal chemistry, including compound design and structure–activity relationship work, is a merit.
• Experience of peptide or peptidomimetic chemistry is a merit.
• Experience of photoredox catalysis or radical chemistry is a merit.
• Experience from the pharmaceutical industry or contract research is a merit.
• A documented ability to publish research results in international peer-reviewed journals.

Consideration will also be given to good collaborative skills, drive and independence, and how the applicant’s experience and skills complement and strengthen ongoing research within the department, and how they stand to contribute to its future development.

Terms of employment

This is a full-time, fixed-term employment of a maximum of two years. The period of employment is determined in accordance with the agreement “Avtal om tidsbegränsad anställning som postdoktor” (“Agreement on fixed-term employment as a post-doctoral fellow”) between Lund University, SACO-S and OFR/S, dated 1st February 2022.

Instructions on how to apply

Applications shall be written in English and be compiled into a PDF-file containing:

• résumé/CV, including a list of publications,
• a general description of past research and future research interests (no more than three pages),
• contact information of at least two references,
• copy of the doctoral degree certificate, and other certificates/grades that you wish to be considered.