Doble lipidmembranrom - cellulære beholdere omsluttet av to myke membraner - er ofte observert i biologiske celler som for eksempel cellekjernen, kloroplaster og mitokondrier. Nylig ble doble membraner observert i nøkkelprosesser som involverer autofagi. Autofagi ('selvspising') er biologiens måte å fjerne skadde celler på for å tillate regenerering av nye, sunne celler. Selv om tidligere forskning har bidratt til å gi et klarere bilde av hvordan molekylærbiologiske aspekter ved autofagi fungerer, gjenstår det fortsatt å besvare noen grunnleggende biofysikkrelaterte spørsmål. For å ta tak i noen av disse spørsmålene, vil vårt tverrfaglige prosjekt samle matematisk modellering, cellebiologi, biomaterialvitenskap og nanoteknologi. Beregningsmodellering vil bidra til å forutsi dobbelmembranadferd, og biomaterialer og nanoteknologi vil bidra til å konstruere doble membraner kunstig - utenfor cellene. Cellebiologi vil forhåpentligvis avsløre hvilke av de biologiske komponentene som er innflytelsesrike i dobbelmembranadferd i sammenheng med autofagi. En tverrfaglig innsats gjør det mulig å tilnærme seg dette forskningsproblemet fra ulike vinkler. Dette er veldig nyttig for komplekse problemer som den vi fokuserer på i dette prosjektet.
In this project we aim to establish how cellular double lipid bilayer vesicles are formed and developed in response to interfacial contacts. As a model concept, we will focus on autophagy, a cellular process that involves elimination of cytoplasmic objects in a double membrane compartment. At a molecular level, the mechanisms leading to the double bilayer vesicles in authophagy are well established, however, the striking membrane transformations have been largely overlooked at the mesoscale, the scale between atoms and cells. In order to address this knowledge gap, we have assembled a team consisting of a world leading molecular cell biologist, two talented early career scientists in applied mathematics and in lipid membrane nanotechnology, as well as state-of-the-art light and electron microscopists. Our approach is to identify and extract key molecules with molecular cell biology, and combine them with model membrane systems to observe isolated effects of the components. The data will be utilized to establish mathematical models which are essential to overcome the technical experimental limitations and to fully characterize the mechanisms involved. Our team previously worked in a thematically unrelated interdisciplinary project and jointly made several breakthroughs reported in some of the most prestigious scientific journals. Our synergy and experience in successfully implementing interdisciplinary research will be beneficial for the proposed project and we are confident that the project will lead to a paradigm change in the understanding of membrane dynamics during the autophagic process. Interference in the autophagy pathway has revolutionary therapeutic potential and we anticipate that some of our results will be relevant for understanding of diseases in which autophagy plays a key role as well as of the understanding of other cellular double membrane structures such as the nuclear envelope, mitochondria, chloroplasts and virus-induced double bilayer vesicles.
