An Experimental View on the Molecular Phase Space

Tidsperiod: 2018-01-01 till 2021-12-31

Projektledare: Tomas Ekeberg

Finansiär: Vetenskapsrådet

Bidragstyp: Bidrag för anställning eller stipendier

Budget: 3 720 000 SEK

Amyloid fibers are associated with more than \num{20} human diseasesranging from diabetes to Alzheimer´s. Still, the initiation of fiberformation has eluded scientists because of the many rapidconformational changes between short-lived states that monomers andshort oligomers undergo.RuBisCo is the protein responsible for carbon fixation in plants and amajor target for protein engineering because of the potentialagricultural application. In many plants, RuBisCo is dependent on theenzyme RuBisCo activase, to restores activity of RuBisCo after beinginactivated by strongly binding inhibitors. The complex formed byRuBisCo and its activase is however short lived and has beenimpossible to interrogate structurally.These are only two examples where fast dynamics play an important rolein biological systems and where our inability to study such systemsprevents research that could benefit many millions of people sufferingfrom for example disease or hunger.X-ray free-electron lasers provide a unique opportunity to capturesuch fast dynamics by providing pulses whose length in time is similarto that of atomic vibrations and data-rates of \num{80} milliondiffraction patterns per day. However, the algorithms needed toidentify individual conformations from these huge and noisy data setsare currently lacking. In this project I aim to develop thesealgorithms and make structural studies of rapidly changingbiomolecules possible at X-ray free-electron lasers.