PhD defence by Philip Mark Lund

On Tuesday 6 June 2023, Philip Mark Lund will defend his PhD thesis "Mechanistic understanding of peptide binding and translocation across native like membrane model systems".

Time: 12:30

Place: Building 303A, auditorium 45 & zoom:  https://dtudk.zoom.us/j/65202052293?pwd=Ymt6RWQ3OEhHVGh4UGFqSUd0NFhJdz09

Please be aware that the PhD defense may be recorded - This will also be informed at the beginning of the PhD defense.

Supervisor: Professor Thomas Lars Andresen
Co-Supervisor: Senior Researcher Jannik Bruun Larsen
Associate Professor Jens Bæk Simonsen

Assessment committee:
Associate Professor Rodolphe Marie, DTU Health Tech

Associate Professor Daniel Wüstner, University of Southern Denmark - Department of Biochemistryand Molecular Biology

Professor Ana J. García-Sáez, University of Cologne – Faculty of Mathematics and Natural sciences

Chairperson:
Associate Professor Jonas Nyvold Pedersen, DTU Health

Abstract:
The application of therapeutic peptides for treating chronic patients sick with diabetes and short bowel syndrome has increased due to their beneficial properties of high efficacy and low side effects. The disadvantage of this class of medicine is the requirement of injection administration, which inflicts discomfort and requires extra attention for the patient at every administration. Therefore, developing an oral administration route for therapeutic peptides is of high interest. Oral administration of therapeutic peptide medicine is available on the market, however, only 1% of the peptide reaches the bloodstream, indicating a lack of investigation in efficient delivery.
The oral administration route for a therapeutic peptide is filled with challenges starting from the acidic stomach and enzyme-degrading environment followed by the small intestines' enzymatic activity. The peptide is then required to transport across the small intestine cell layer into the bloodstream to deliver a medical effect.
This thesis work has focused on developing experimental setups to understand the transport of peptides across cell membranes to apply these insights to develop efficient oral administration of peptides. I developed a microscopy setup capable of presenting the specific molecular mechanism across membranes, while another was capable of delivering a rapid indication of possible molecular mechanisms. Lastly, in collaboration, I developed a polymer that displayed advantageous properties for carrying peptides and enhancing their transport across membranes. Further investigations of this polymer are being performed in the search to enhance oral peptide administration. The knowledge created in this thesis will hopefully aid in further development in oral administration and inspire novel ideas.