PhD candidates | Development of new intervention strategies to combat Mycobacterium tuberculosis, the Netherlands
The department of Medical Microbiology and Infection Control (MMI) of the VU medical center has great expertise in bacterial protein secretion systems and using these systems to understand host-pathogen interactions and vaccine development. The section is embedded within the Amsterdam Infection & Immunity Institute (AI&II), which focuses on fundamental molecular research that will lead to breakthroughs in the development of novel therapeutics and molecular diagnostics. The drug discovery project will be funded by a NACTAR grant from the Applied and Engineering Sciences (TTW NWO) to Professor Wilbert Bitter, Eelco Ruijter (PhD) and Alex Speer (PhD) and the duration is 4 years. The vaccine discovery project will be funded by the CCA granted to Coen Kuijl (PhD), Professor Yvette van Kooyk and Professor Wilbert Bitter for the duration of 4 years.
- You have or will soon obtain a MSc degree in molecular biology, biomedical sciences, biochemistry or related fields;
- You are interested in research in the field of microbiology;
- You are a talented, ambitious and highly motivated researcher, who is curious, a team player and has organization skills;
- You have excellent communication skills in English.
Mycobacterium tuberculosis is the causative agent of tuberculosis (TB) and estimated to be responsible for the death of 1.5 million people each year. These daunting figures from the WHO seem to conflict with the fact that tuberculosis can be cured with antibiotics. One of the problem is that, in the last decades, there has been a steady rise in the number of TB cases with drug resistant TB. Therefore, the discovery and development of a vaccine and novel drugs against mycobacteria is a major priority. However, development of new intervention strategies is not easy and will be the challenge you will take on:
- Position 1
One PhD candidate aims at finding novel drugs against mycobacteria. M. tuberculosis is a persistent bacterium with an unusual and highly impermeable cell envelope that protects the bacterium from antibiotics. To secrete proteins across this cell envelope, mycobacteria use specialized secretion systems known as type VII secretion (T7S). Using a whole cell-based high throughput screening campaign we succeeded to identify new classes of small molecules that inhibit T7S secretion. Moreover, some of these compounds reduced significantly the bacterial burden in zebrafish larvae infected with pathogenic mycobacteria. In this proposal, we will combine synthetic and medicinal chemistry with biochemistry and microbiology to study the newly identified T7S inhibitors in more detail. One goal is to identify the target for these compounds. Another goal is to perform lead development by testing derivatives in a zebrafish infection model for increased activity. In this project we closely collaborate with the department of synthetic chemistry of the VU (Eelco Ruijter, PhD), who will employ a synthetic chemist (postdoc) on the same project.
- Position 2
The other PhD candidate aims at harnessing the immunological properties of Mycobacterium bovis BCG for vaccine and bladder cancer therapy purposes. Mycobacterium BCG is attractive as a vaccine vector because of its extensive safety record in humans (BCG), heat stability and low production cost. Moreover they have adjuvant activity and can be administered via oral administration, including to newborns. BCG is however a poor vaccine against tuberculosis itself and recent efforts to enhance immunogenicity of BCG led to increased pathogenicity. With the recently discovered protein coupling tools we are able to decorate bacteria with proteins to display relevant immunogenic epitopes and enhance their targeting to specific cell types. With this approach we aim to develop a new vaccine for M. tuberculosis and enhance the current bladder cancer therapy. In this project we closely collaborate with the department of Molecular Microbiology of the VU (Joen Luirink, PhD) and with the department of Molecular Cell Biology and Immunology of the VUmc (Professor Yvette van Kooyk).
The selected candidates will be offered:
- A stimulating working environment in one of the leading groups on protein secretion in mycobacteria with key collaborations in the field of synthetic chemistry, infection biology and structural biology;
- An opportunity to do research that will make a difference in the tuberculosis field.
The appointment will be for a period of 1 year with potential for extension to a total duration of 4 years
If you’re interested about this position, you can contact prof. dr. Wilbert Bitter, via telephone number 020 444 8319. If you need more information about the application procedure, contact Evelien Hoozemans, corporate recruiter at 020- 444 5635.