PhD candidate experimental translational pharmacology in infectious diseases

Project description
Tuberculosis causes 1.5 million deaths yearly and anti-tuberculosis therapies are threatened by emergence of drug resistance. Development of innovative drug combinations should be accelerated with the use of translational pharmacological models. Moreover, host-directed therapies (HDT), which stimulate the immune system to clear the infection, are suggested as complementary strategy to antibiotics, to improve treatment outcomes and shorten treatment duration. In addition to existing murine disease models, the zebrafish larva is an attractive model organism to study infectious disease and their interplay with the immune system and therapies, earlier in drug development. A TB disease model has been established based on Mycobacterium marinum infection through different routes, with serial fluorescence microscopy observations of both bacteria and immune cells to study their response to infection and treatment. Proof-of-concept of translatability of pharmacokinetics-pharmacodynamic findings from zebrafish larvae to higher vertebrates has been shown for anti-TB drugs such as isoniazid [Van Wijk et al, BJP 177(24), 2020].

The PhD candidate will consolidate the translational pharmacokinetic-pharmacodynamic workflow with additional antibiotics by pharmacokinetic and pharmacodynamic experiments, including exposure-time experiments in whole-organism and nanoscale blood sampling, and response experiments with fluorescence microscopy. The translational workflow will be expanded to study and quantify HDT and their interaction with pathogen and treatment through biomarker analysis, such as cytokines, immune cells, genetic, or (fluorescence) microscopy. The PhD candidate will closely work with group members with computational backgrounds within the spirit of Team Science. With this work, development of optimal HDT-based treatment strategies against tuberculosis will be supported.

Key responsibilities

• Conduct original, novel, and collaborative research in the framework of the project and complete your PhD thesis within 4 years;
• Publish scientific articles at international peer-review journals;
• Present at national and international conferences;
• Support education activities in the bachelor and master programs of biopharmaceutical sciences;
• Engage in collaborations between internal and external research groups;
• Follow PhD courses based on an individual training and supervision plan.

Requirements

• A Master’s degree in a bio-pharmaceutical or biomedical sciences, (computational) biology, life sciences or a related field with a strong quantitative focus
• Practical experience in

1. pharmacological (e.g. concentration-time-, concentration-effect experiments);
2. microbiological (e.g. infection studies, OD/CFU biomarkers, time-kill);
3. preclinical experimental (e.g zebrafish infectious disease models, or murine disease models);
4. analytical chemical (e.g. LC/MS assay);
5. biomedical (e.g. (fluorescence) microscopy incl. image analysis, flow cytometry); and/or
6. molecular biology (e.g. PCR) experimental work

• Full proficiency in English
• Strong communication skills and affinity to present/visualize complex data/findings
• Ability to work independently and in teams
• Excellent organisational and planning skills
• Interested in participating in educational tasks

Preferred skills

• Experience in or affinity with immunology and/or immunopharmacology
• Experience in or affinity with PK-PD, QSP, and/or PBPK modelling, or mechanistic biological modelling
• Experience in or affinity with computational languages (e.g. R, NONMEM)

Terms and conditions
We offer a full-time appointment of initially one year. After a positive evaluation of the progress of the research, teaching evaluations, personal capabilities and compatibility, the appointment will be extended for another three years. You will be appointed in accordance with the Collective Labour Agreement for Dutch Universities. The salary ranges from € 2.770,- per month in the first year to € 3.539,- gross per month in the fourth year based on a full-time position (pay scale P).

Leiden University offers an attractive benefits package with additional holiday (8%) and end-of-year bonuses (8.3 %), training and career development. Our individual choices model gives you some freedom to assemble your own set of terms and conditions. For international spouses we have set up a dual career program. Candidates from outside the Netherlands may be eligible for a substantial tax break. For more information, see the website: https://www.universiteitleiden.nl/en/working-at/job-application-procedure-and-employment-conditions.

All our PhD students 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. In addition, advanced courses to deepen scientific knowledge are offered by the research school.

Diversity and work-life balance
Leiden University is strongly committed to diversity within its community and especially welcomes applications from members of underrepresented groups. LACDR is a highly diverse institute, in culture, background, and gender. We stand for excellence in a caring Institute. We wish to reflect society in all aspects, as we believe that this improves the dynamics in our organization. Therefore, we support and understand the need for a work/life/family balance and consequent varying working hours and places. We believe that doing good science is fun, and goes hand in hand with a friendly culture.

Our organization
Working at the Faculty of Science means being part of an exciting, dynamic scientific environment which sets high standards for its students and staff. The research carried out at the Faculty of Science is diverse, ranging from computer science, mathematics, astronomy, physics, chemistry and bio-pharmaceutical sciences to biology and environmental sciences.

The faculty has grown strongly in recent years and now has more than 2,300 staff and over 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. For more information, see https://www.universiteitleiden.nl/en/science.