PhD ceremony Ms. G. Moiset Coll: Molecular basis of membrane stability and dynamics

PhD ceremony: Ms. G. Moiset Coll

Dissertation: Molecular basis of membrane stability and dynamics

Promotor(s): prof. B. Poolman

Faculty: Mathematics and Natural Sciences

Gemma Moiset Call studeerde medische chemie en moleculair design aan de universiteit van Girona, Spanje. Haar promotieonderzoek deed zij aan de RUG, bij de afdeling Biochemistry van het Groningen Biomolecular Sciences and Biotechnology Institute (GBB). Het maakt daar deel uit van het synthetische-biologieproject. Het onderzoek werd gefinancierd door het Zernike Institute for Advanced Materials (ZIAM) van de RUG.

The first important result of Gemma Moiset Coll was unrevealing the mechanism of action of small antimicrobial entities that serve as antibiotic alternative to pathogens that affect plant crops. The second important finding is the effects of sugars on the organization of artificial cell membranes. That could be the clue for the survival of organisms under desiccation conditions.

The thesis of Moiset covers four topics centered around the interactions between cell membranes and other biological molecules including antimicrobials, sugars, channels and transporters. Chapters 2–4 describe studies into the mechanism of action of antimicrobial peptides. Moiset focused on two short peptides, the cyclic BPC194 and its linear analogue BPC193. Despite having the same amino acid sequence, only the cyclic peptide is able to kill microbial cells. Using a combination of fluorescence-based techniques and molecular dynamic simulations, we were able to visualize the stages involved in pore formation and membrane fusion. In chapter 5, Moiset synthesized a DNA-peptide hybrid designed to modulate the oligomerization of a membrane channel using complementary DNA strands or a G-quadruplex motif. In both cases, the resulting channel had a preference for one specific oligomeric state of a fixed size. In chapter 6 Moiset investigated the effects of carbohydrates on membrane organization. She combined fluorescence microscopy with molecular dynamic simulations and found out that only the non-reducing carbohydrates, sucrose and trehalose, have an effect on lipid raft organization. These two disaccharides are synthesized by various organisms in order to survive in extreme desiccation conditions. In chapter 7 Moiset studied the localization, oligomerization and dynamics of different plasma membrane amino acid transporters of Saccharomyces cerevisiae. The distribution of these proteins in the membrane is not homogeneous. She hypothesizes that the reason might be the extremely slow diffusion that she measured for those proteins, together with their low amounts.