“Smart antibiotics by design of molecular switches for red-light control of antibiotic activity and biofilm formation”
Photopharmacology is a rapidly emerging field at the interface of the chemical and medical sciences aiming at high precision therapy. Being among the founding fathers of photopharmacology (together with the Trauner group at NY University), our expertise in molecular photoswitches and light-driven rotary motors gives us a unique advantage to design the smart medicine of the future. Unlike optogenetics, widely used in neuroscience relying on genetic modification of the organism, the basis for photopharmacology is the design of drugs with intrinsic switchable functions. Specifically, this means that in bioactive molecular components (common pharmaceuticals) designed with intrinsic light-switchable units, the biological activity can be switched on and off with high precision on command using light. The use of light as external trigger allows high precision activation of a drug in space and time in a non-invasive manner. This opens fascinating opportunities for precise targeting of e.g. tumors, and bacterial infections. High precision cancer chemotherapy, fighting bacterial resistance or infectious biofilms are among the prospects for future clinical applications. In a more fundamental scientific perspective control of specific pathways in complex biological networks open numerous opportunities. Our Nobel prize winning research on molecular machines (light-driven chiral molecular switches and motors) introducing directional motion at the nanoscale enabled us to explore the basic principles of photopharmacological agents. We pioneered photoswitchable antibiotics and quorum sensing molecules, interfering with bacterial communication and very recently demonstrated the regulation of the circadian clock in human cells.

A major scientific question that we plan to address is: can we design photoswitchable antibiotics the activity which can be controlled by near infrared (IR) light? This addresses the fundamental questions how to make biocompatible molecular photoswitches that allow high tissue penetration, use non-toxic irradiation and combine imaging with on spot activation.

The PhD student will focus on smart antibiotics especially addressing the issues of tissue penetration and orthogonality i.e. imaging and activation. Towards this goal novel red-light based photoprotecting groups (PPG) and photoswitches will be explored and incorporated into diverse antibiotics. Recently, based on preliminary computational and experimental studies, we have designed new PPG’s and switches (azobenzenes, thioindigo’s, stiff-stilbenes) that responsive to light in the therapeutic window. These systems form an excellent basis to incorporate into antibiotics either as intrinsic or as pending photoresponsive units. Furthermore, the combination of imaging and switching for direct theranostic applications is hardly explored. Precise control of orthogonal photochemical effects will allow a major step toward in situ imaging (especially PET/fluorescence) and high precision activation.

We are looking for candidates who meet the following requirements:

- a MSc degree in chemistry or a related field
- experience in synthesic organic chemistry
- the ability to work independently
- excellent grades
- creativity, determination and motivation.

Experience in medicinal chemistry, chemical biology and/or spectroscopy is a plus.

Applicants whose first language is not English must submit evidence of competency in English, please see University of Groningen’s English Language Requirements for details.

Fixed-term contract: 48 months.

We offer you in accordance with the Collective Labour Agreement for Dutch Universities:

- a salary of € 2,541 gross per month in the first year, up to a maximum of € 3,247 gross per month in the fourth and final year, based on a full-time position (1.0 FTE)
- a holiday allowance of 8% gross annual income
- an 8.3% year-end bonus
- a position for four years; you will get a temporary position of one year with the option of renewal for another three years; prolongation of the contract is contingent on sufficient progress in the first year to indicate that a successful completion of the PhD thesis within the next three years is to be expected
- a university PhD training programme is part of the agreement and the successful candidates will be enrolled in the Graduate School of Science and Engineering.

The starting date is flexible

Faculty of Science and Engineering

The University of Groningen is a research university, currently in or around the top 100 on several influential ranking lists. The Faculty of Science and Engineering (FSE) is the largest faculty within the University, offering first-rate education and research in a wide range of science and engineering disciplines.

The mission of the Stratingh Institute for Chemistry is to perform excellent research and teaching in molecular and supramolecular chemistry. Core activities in the chemical sciences such as bioorganic chemistry, organic chemistry, molecular inorganic chemistry and molecular materials chemistry are embedded in the institute. The research programme is focused on synthesis, catalysis, functional materials, bio-organic chemistry/chemical biology and systems chemistry/complex molecular systems.

The research program of the Feringa group is focused on synthetic and physical organic chemistry. Inspired by Nature's principles of molecular assembly, recognition, transport, motion and catalysis, the goal is to exploit the full potential of synthetic chemistry to create new structures and functions. A major part of the research is directed towards dynamic molecular systems. The focus is on molecular nanoscience, novel responsive materials and photo-pharma exploring biohybrid systems, self-assembly, molecular switches and motors. A second part of the program deals with the development (and application in chemical biology) of novel stereoselective synthesis methods and asymmetric catalysis. Chirality is a leading theme and over the years a unique and broad expertise in fundamental aspects of stereochemistry has been acquired including chiroptical phenomena, chiral amplification and origin of chirality.