PhD candidate || Virtual screening combined with chemical proteomics to globally profile new targets for antibiotics (1.0 fte)

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The Faculty of Science and the Leiden Institute of Chemistry are looking for a:
PhD candidate || Virtual screening combined with chemical proteomics to globally profile new targets for antibiotics (1.0 fte)
Vacancy number: 22-405

Project description
Antibiotic-resistant bacterial infections have directly caused more than 1.2 million deaths in 2019, making the identification of new antibiotics an important priority. Covalent inhibitors are already very successful as antibiotics and we have recently identified many new covalently ligandable binding sites in bacteria using competitive residue-specific proteomics with 20 covalent ligands. We now aim to utilize this dataset as a starting point for a first-in-class proteome-wide covalent virtual screening campaign, where we will predict the interaction landscape of an in-house >10,000-member covalent ligand library against >300 cysteines in essential proteins of S. aureus. Using biochemical assays for specific proteins, we will validate the performance across the entire library and using competitive residue-specific proteomics, we will assess the accuracy of the proteome-wide predictions. In this way, we will generate a large interaction landscape for covalent inhibitors targeting many high priority antibiotic targets and deliver promising starting points for antibiotic development. Furthermore, we will deliver a robust proteome-wide virtual screening platform that will be available for many additional projects that aim to identify covalent inhibitors targeting diverse protein classes for various biological applications.

Selection criteria
•    MSc degree in Chemistry, Life Sciences, Pharmaceutical Sciences, or similar, with a passion for computational modeling and drug discovery;
•    Excellent proficiency in English;
•    Wet-lab biochemical experience;
•    Intermediate Python experience for the automation of simulations and their analysis;
•    Other desirable skills: experience with molecular docking, further development programming skills, experience with Linux and large-scale computing facilities.

Our organisation
The Faculty of Science is a world-class faculty where staff and students work together in a dynamic international environment. It is a faculty where personal and academic development is top priorities. Our people are committed to expand fundamental knowledge by curiosity and to look beyond the borders of their own discipline; their aim is to benefit science, and to make a contribution to addressing the major societal challenges of the future.
The research carried out at the Faculty of Science is very diverse, ranging from mathematics, information science, astronomy, physics, chemistry and bio-pharmaceutical sciences to biology and environmental sciences. The research activities are organized in eight institutes. These institutes offer eight bachelor’s and twelve master’s programs. The faculty has grown strongly in recent years and now has more than 2,300 staff and almost 5,000 students. We are located at the heart of Leiden’s Bio Science Park, one of Europe’s biggest science parks, where university and business life come together.

The chemistry and life science research in the Leiden Institute of Chemistry (LIC) is organized around two major research areas: ‘Chemical Biology’ and ‘Energy & Sustainability’. The institute’s research themes illustrate the central position of chemistry between biology, medicine and physics. The various research topics carried out within these themes are ideal for executing interdisciplinary research.

Terms and conditions
We offer a full-time position for initially one year. After positive evaluation of the progress of the progress of the thesis, personal capabilities and compatibility the appointment will be extended by a further three years. Salary range from € 2.540 to € 3.245 gross per month (pay scale P in accordance with the Collective Labour Agreement for Dutch Universities).
Leiden University offers an attractive benefits package with additional holiday (8%) and end-of-year bonuses (8.3 %), training and career development and sabbatical leave. Our individual choices model gives you some freedom to assemble your own set of terms and conditions. Candidates from outside the Netherlands may be eligible for a substantial tax break.

All our PhD candidates are embedded in the Leiden University Graduate School of Science. Our graduate school offers several PhD training courses at three levels: professional courses, skills training and personal effectiveness. 

Diversity
Diversity and inclusion are core values of Leiden University. Leiden University is committed to becoming an inclusive community which enables all students and staff to feel valued and respected and to develop their full potential. Diversity in experiences and perspectives enriches our teaching and strengthens our research. High quality teaching and research is inclusive.

Information
If you have any questions regarding the application procedure, please contact Jessica van Krimpen-Kraaijenoord (management assistant), [email protected] .  Enquiries related to the project can be made to Dr. Anthe Janssen, [email protected] ,  or Dr. Stephan Hacker, [email protected] . 

Applications
Please send your application to Jessica van Krimpen-Kraaijenoord, [email protected]  including the following documents:
•    A letter of motivation;
•    An updated CV;
•    Copy of master’s thesis or any other publication (if available);
•    The (preliminary) transcripts of your MSc studies and copy of your degree;

Application deadline is 30 October 2022. Applications will be considered on a rolling basis.

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