In this project, the candidate will work on a multidisciplinary project in collaboration with international collaborators. The goal is to develop a photoswitchable antibody that can be used for the treatment of rheumatoid arthritis (RA).
Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells into the synovial membrane within the joints with concomitant production of pro-inflammatory cytokines. Current medication relies on the administration of methotrexate and antibodies against these pro-inflammatory cytokines. Because this medication inhibits the immune system through the entire body and not only at the sites of RA related inflammation, the patients suffer from an increased risk towards infections.
In this project, you will develop a new line of treatment for RA, which inhibits the immune system more selectively. To this end, you will express in E. coli antibody fragments containing a cysteine mutation close to the antigen binding site. In a second part of the project, you will synthesize a chemical linker containing a photoswitchable linker, a bulcky group and a malemide functionality for conjugation to the antibody fragment. By conjugating this linker close to the antigen-binding site we anticipate to control the position of the bulcky group using light as a spatiotemporal switch. Using light of a specific wavelength will position the bulcky group close to the antigen-binding site thereby preventing binding of the cytokine and thus inactivating the antibody. Upon irradiation with a different wavelength, the bulcky group pivots away and binding of the cytokine is enabled.
As such, the affinity of the antibody fragment can be modulated using visible light. In practice this would mean that sites of RA related inflammation can selectively be irradiated to turn on the antibody fragment there where it is needed. This project requires a strong interest and knowledge on protein expression and organic chemistry.The first goal is to obtain synthetic layers that can recognize and bind the bacteria. Following, these layers will be incorporated into a sensor in order to characterize them in terms of sensitivity and selectivity. Moreover, the project includes the exploration of the sensor in potential application fields such as environmental monitoring, health diagnosis or food safety.
Research within the Sensor Engineering research group at the Faculty of Science and Engineering of Maastricht University is focused on developing innovative sensor technologies for implementation in diverse fields ranging from medical diagnostics to food safety assessment. For this position, we are looking for a motivated PhD student with a master degree and a solid background in bio-, organic, polymer or analytical chemistry. The candidate will work in a multicultural, interdisciplinary team consisting of engineers, chemists and biomedical scientists. The research group has developed extensive expertise in combining sensor technology with chemistry and biomedical engineering to acquire knowledge and streamline applications for use in real life settings.
As a PhD student your tasks include:
- Lead your own research project independently (although supervision by expert researchers will be provided)
- Study literature
- Develop research plan
- Experimentation and data processing
- Scientific Dissemination: writing articles and participating in international conferences
- Contribute to the teaching activities of the department, mostly as a tutor or lab supervisor