- E-postoyvind.halskau@uib.no
- Telefon+47 55 58 45 63
- BesøksadresseThormøhlens gate 53 A/B5006 BergenRom521B
- PostadressePostboks 78035020 Bergen
Membraner som katalysatorer i proteinmisfoldingLivets enhet er cellen. Den er avgrenset av cellemembranen, en tynn barriere på bare noen få nanometer. Dette er ikke en fast barriere, men snarere en halvflytende oljeaktig affære. Den består av lipider, molekyler som slekter på fettstoffer eller oljer, samt proteiner. Det er også kjeder av sukkermolekyler knyttet til membranen. Cellemembranen tillater noen molekyler å passere gjennom seg, men er ugjennomtrengelig for andre. Mange av cellemembranens bestanddeler -- både proteiner, lipider og sukkermolekyler -- er godt forstått med hensyn på individuelle egenskaper og funksjon. Men i det komplekse og stadig skiftende miljø i en cellemembran har det så langt vært en utfordring å forstå hvordan hver komponent kan påvirke hverandre. Å forstå dette samspillet er avgjørende for også å kunne forstå cellens molekylære fundament. Dette prosjektet vil undersøke hvordan lipider påvirker proteiner og hvordan proteiner påvirke integriteten av lipidene som gir cellemembranen sin integritet som barriere. En av de viktigste spørsmålene er hvorvidt noen lipider eller fysiske tilstander av membranen kan føre til at visse proteiner mister sine struktur. Proteiner vil normalt trenge å ha en bestemt struktur, eller fold som det kalles, for å oppnå sin biokjemiske funksjon. Dersom denne vanligvis spontane prosessen blir forstyrret kan proteiner danne skadelige tilstander i stedet. Dette er normalt kalt protein misfolding. Prosjektet stiller spørsmål om noen lipider kan forårsake misfolding hos visse membranassosierte proteiner i et raskere tempo enn det ellers ville skje. Slike misfoldingshendelser er implisert i mange sykdommer, inkludert Parkinsons, Alzheimers og diabetes II, samt prionsykdommer. Hvis det vitenskapelige spørsmålet er godt stilt og prosjektet klarer å følge det opp med riktige teknikker er det mulig at man kan få ny og detaljert innsikt i sykdomsmekanismer. Dette kan på sikt føre til bedre forebygging eller behandling. Preliminære funn tyder på at cells foretar store forandringer i lipidsammensetningen sin gjennom livssyklusen sin. Lipidsammensetningene er så forskjellige at dette fører til endringer i cellemembranens fysiske egenskaper. Vi ser også at forskjellige lipidsammensetninger påvirker aggregeringsraten til peptidmodellsystemer.
Dette prosjektet er bevilget av Forskningsrådets prosjekt#240063 og støttes også av Bergen Medisinske Forskningsstiftelse.
Kromatinorientert genregulering og cellenes minne
Denne problematikken er utarbeidet av Rein Aasland, og vårt bidrag er å hjelpe til å forstå strukturen og dynamikken til proteiner som gjenkjenner metyleringer på histoner. Dette arbeidet gjøres ved hjelp av høyoppløselig NMR. Se Reins egne sider for mer informasjon. Genetisk informasjon er lagret i DNA’et i genomet vårt. DNA er pakket og strukturert på forskjellige vis, og proteinkomplekset kromatin er en del av denne pakkingen. Men kromatinet kan også bære informasjon som er viktig for hvordan gener blir uttrykket (eller ikke). Denne informasjonen er lagret i form av biokjemiske modifiseringer på histoner, som sammen med DNA’et det pakker danner nukleosomer. Repeterende nukleosomer utgjør så kromatinet. Hvordan kromatinet bærer informasjon, både som følge av modifikasjoner og som følge av hvordan det pakker og tilgjegeligjør DNA er ubesvarte spørsmål.
Enteroteoksigenisk Esherichia coli (ETEC)
Vi har også et lite bidrag inn mot vaksineutviklingsprosjektet ETECvac, hvor vi også bidrar med NMR-ekspertise:
ETEC overføres via feces, for så å kolonisere tynntarmen. Bakteriens adhesjon til tarmepitelet er styrt av koloniseringsfaktorer og proteinstrukturer på bakterieoverflaten. ETEC sekrerer varmestabile og varmelabile enterotoksiner som forårsaker stor sekresjon av salter og vann, noe som resulterer i diaré. I verste fall får pasienten en koleralignende tilstand. Igjen dreier vårt bidrag seg rundt å karakterisere struktur og dynamikk til de sekrerte faktorene ved hjelp av NMR. Vi vil også karakterisere interaksjonsflater mellom toksinene og en av tynntarmens reseptorer, samt antistoffer. Dette er et (av flere) nødvendige steg for å lage en vaksine som ikke er sykdomsfremkallende, men allikevel forårsaker en immunrespons.
MOL310 Strukturell Molekylærbiologi
Målet for emnet er å gi studentene kunnskap om forholdet mellom biomakromolekylers struktur og funksjon.
MOL270 Bioetikk
Dette kurset underviser og organiserer jeg sammen med Anders Goksøyr og Gyri Haugland.
MOL210 Lipidbiokjemi
Dette kurset, som jeg underviser sammen med Aurelia Lewis, er ment å gi studenten en fordypning i lipiders kjemiske, cellulære og patologiske egenskaper.
MOL200 Metabolisme
Her underviser jeg i Aminosyrekjemi og syntese
Tidligere kurs:
MOL320 Avanserte Metoder i Biokjemi
Dette kurset gir studentene en praktisk innføring med noe tilhørende teori i biofysikalske metoder som er tilgjengelig ved Molekylærbiologis Institutt. Kurset er modulbasert og bygget rundt praktisk laboratoriearbeid og dataanalyse. Eksempler på moduler som gis er: Surface Plasmon Resonance, Isothermal Calorimetry, Fluorescence og Protein NMR.
Mindre undervisningsbidrag:
2015: MBV 9520 (2x45 min forelesning i proteindynamikk, BIOSTRUCT-kurs på nasjonalt nivå)
2014, 16, 18, 20: MOL950 (en bitteliten praktisk NMR-modul, BIOSTRUCT-kurs på nasjonalt nivå)
2011-13: Forelesning (2x 45 min, biokjemi og kolloidkjemi) i BMED325 ‐ Nanobiokjemi
2012: Forelesning in Atomic Force Microscopy (1 x45 min, BIOSTRUCT-kurs på nasjonalt nivå)
2007‐11: Forelesninger og diskusjoner i BMED310 ‐ Vitenskapsfilosofi
1998‐2001: Statistikk (SOK33B) og Uorganisk Kjemi (K102)
Her er min akamdeiske produksjon som vist i:
Under finner du også publikasjonene mine i CRIStin. Det er stort overlapp mellom disse databasene, men de har litt forskjellige inklusjonskriterier og oppdateringsrutiner.
- (2023). The high-resolution cryo-EM structure of vitellogenin from the hemolymph of the honey bee.
- (2023). Phospholipid membrane interactions of model peptides and depth of insertion investigated via solid-state NMR.
- (2023). Contrasting the phospholipid profiles of two neoplastic cell lines reveal a high PC:PE ratio for SH-SY5Y cells relative to A431 cells. Biochemical and Biophysical Research Communications - BBRC. 23-29.
- (2022). Resolving the zinc binding capacity of honey bee vitellogenin and locating its putative binding sites. Insect molecular biology (Print). 810-820.
- (2022). How Honey Bee Vitellogenin Holds Lipid Cargo: A Role for the C-Terminal. Frontiers in Molecular Biosciences. 8 sider.
- (2022). Binding Specificity of ASHH2 CW Domain Toward H3K4me1 Ligand Is Coupled to Its Structural Stability Through Its α1-Helix. Frontiers in Molecular Biosciences. 1-16.
- (2021). The biosynthesis of phospholipids is linked to the cell cycle in a model eukaryote . Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids.
- (2021). Structure prediction of honey bee vitellogenin: a multi-domain protein important for insect immunity. FEBS Open Bio. 51-70.
- (2021). Investigating the Disordered and Membrane-Active Peptide A-Cage-C Using Conformational Ensembles. Molecules. 3607.
- (2020). The Attenuating Effects of 14-3-3eta in Parkinson’s Disease-Related alpha-Synuclein Aggregation.
- (2020). The Arabidopsis (ASHH2) CW domain binds monomethylated K4 of the histone H3 tail through conformational selection. The FEBS Journal. 4458-4480.
- (2020). Senescence-Related Changes to the Lipid Composition of SH-SY5Y Cells with Implications for α-Synuclein Misfolding.
- (2020). Plasma-derived exosome-like vesicles are enriched in lyso-phospholipids and pass the blood-brain barrier. PLOS ONE. 1-15.
- (2020). Phosphorylated TH hinges with vesicular membrane proteins for axonal transport.
- (2020). Lipiders rolle i nevrodegenerative sykdommer. NBS-nytt.
- (2020). Conformational selection in histone binding – when being rigid fails.
- (2020). Cholesterol-containing lipid nanodiscs promote an α-synuclein binding mode that accelerates oligomerization. The FEBS Journal.
- (2020). Bioactive metabolites of marine origin have unusual effects on model membrane systems. Marine Drugs. 1-11.
- (2019). Neuronal cell lipidomics and role of cholesterol in α-synuclein binding and aggregation.
- (2019). Neurodegenerative sykdommer -- proteinkrøll gir hjernekrøll.
- (2019). Misfolding i neurodegenerative sykdommer.
- (2019). From potent toxin to vaccine toxoid: Engineering the enterotoxigenic Escherichia coli heat-stable toxin into a subunit vaccine component.
- (2019). Fast and quantitative phospholipidomic analysis of SH-SY5Y neuroblastoma cell cultures using LC-MS/MS and 31P NMR. ACS Omega. 21596-21603.
- (2018). Proteiner og nevrodegenerative sykdommer.
- (2018). Contrasting cellular lipid states using quantitative 31P NMR and LC MS/MS .
- (2018). CW-domain of ASHH2 methyltransferase: structural basis of ligand binding and specificity.
- (2018). Alpha-synuclein oligomerization in the presence of the cholesterol and glycerophosphoglycerol.
- (2018). A novel exosome-like nanocarrier for treatment of refractory epilepsy .
- (2018). A novel exosome-like nanocarrier for treatment of refractory epilepsy .
- (2018). A novel exosome-like nanocarrier for treatment of refractory epilepsy .
- (2018). A biophysical study on the mechanism of interactions of DOX or PTX with α-lactalbumin as a delivery carrier. Scientific Reports. 1-21.
- (2018). 1H, 13C, and 15N resonance assignments of CW domain of the N-methyltransferase ASHH2 free and bound to the mono-, di- and tri-methylated histone H3 tail peptides. Biomolecular NMR Assignments. 215-220.
- (2017). Spectroscopic and AFM characterization of polypeptide-surface interactions: Controls and lipid quantitative analyses. Data in Brief. 113-122.
- (2017). Peptides derived from α-lactalbumin membrane binding helices oligomerize in presence of lipids and disrupt bilayers. Biochimica et Biophysica Acta - Biomembranes. 1029-1039.
- (2017). Lecture on the Nobel Prize of Chemistry 2017 (Cryo-EM).
- (2017). Evidence that Listeria innocua modulates its membrane's stored curvature elastic stress, but not fluidity, through the cell cycle. Scientific Reports. 1-11.
- (2017). Does the lipid fractio of Listeria innocua change as a function of the cell cycle?
- (2016). Why is HAMLET more toxic to dividing cells?
- (2016). The protein, fatty acid and lipid components in early stages of PFA/HAMLET-induced cell death.
- (2016). Reversible protein membrane interactions by mobile peptides.
- (2016). Relevance of the protein, fatty acid and lipid component in early stages of HAMLET induced cell death.
- (2016). Molecular Characteristics of Peptide-Fatty Acid Complex Relevant for Tumoricidal HAMLET.
- (2016). Expression and purification of misfolding peptides from E. coli for spectroscopic characterization.
- (2016). Detection of misfolded protein aggregates from a clinical perspective. Journal of Clinical and Translational Research. 11-26.
- (2016). Detection of Misfolded Protein Aggregates from a Clinical Perspective. Journal of Clinical and Translational Research. 11-26.
- (2016). Characterization of protein-fatty acid complexe.
- (2015). α-lactalbumin: oleic acid complex spontaneously delivers oleic acid to artificial and erythrocyte membranes. Journal of Molecular Biology (JMB). 3177-3187.
- (2014). Two homologous neutrophil serine proteases bind to POPC vesicles with different affinities: When aromatic amino acids matter. Biochimica et Biophysica Acta - Biomembranes. 3191-3202.
- (2014). The N-terminal sequence of tyrosine hydroxylase is a conformationally versatile motif that binds 14-3-3 proteins and membranes. Journal of Molecular Biology (JMB). 150-168.
- (2013). Vitellogenin recognizes cell damage through membrane binding and shields living cells from reactive oxygen species. Journal of Biological Chemistry. 28369-28381.
- (2013). Tunable photophysical properties, conformation and function of nanosized protein–gold constructs. RSC Advances. 482-495.
- (2013). HIV-1 p6 - a structured to flexible multifunctional membrane-interacting protein. Biochimica et Biophysica Acta - Biomembranes. 816-823.
- (2013). Cytotoxicity of bovine alpha-lactalbumin: Oleic acid complexes correlates with the disruption of lipid membranes. Biochimica et Biophysica Acta - Biomembranes. 2691-2699.
- (2013). CREATING BAMLET USING ALPs AND INVESTIGATING THEIR EFFECT ON DIFFERENTIATED AND NONDIFFERENTIATED HUMAN BREAST CANCER CELLS.
- (2013). Anticancer Activity from Gold-alpha-Lactalbumin Nanoconstructs? Journal of Physical Chemistry C. 2230-2238.
- (2012). The peripheral binding of 14-3-3gamma to membranes involves isoform-specific histidine residues. PLOS ONE.
- (2012). PR3 Interacts Directly to Lipid Bilayers: Evidence from MD Simulations and SPR Experiments.
- (2012). PR3 Interacts Directly to Lipid Bilayers: Evidence from MD Simulations and SPR Experiments. Biophysical Journal. 497A-497A.
- (2012). Interactions between BSA-gold nanoparticle constructs and a phospholipid monolayer.
- (2012). HAMLET forms annular oligomers when deposited with phoshpolipid monolayers. Journal of Molecular Biology (JMB). 90-102.
- (2012). Generally applicable procedure for in situ formation of fluorescent protein-gold nanoconstructs. RSC Advances. 11704-11711.
- (2012). An x-linked infantile lethal disorder caused by N-terminal acetyltransferase deficiency.
- (2012). A vitellogenin polyserine cleavage site: highly disordered conformation protected from proteolysis by phosphorylation. Journal of Experimental Biology. 1837-1846.
- (2011). The binding of 14-3-3 gamma to membranes studied by intrinsic fluorescence spectroscopy. FEBS Letters. 1163-1168.
- (2011). Teaching old proteins new tricks.
- (2011). Social pleiotropy and evolution of honey bee vitellogenin. Molecular Ecology. 5111-5113.
- (2011). Mechanism for tunable protein deposition onto charged monodisperse polymer nanoparticles.
- (2011). Interactions of α-Lactalbumin and Cytochrome с with Langmuir Monolayers of Glycerophospholipids. Journal of Dispersion Science and Technology. 150-158.
- (2011). Immobilizaton onto gold nanoparticles alters α-lactalbumin interaction with pure and mixed phospholipid monolayers. Soft Matter. 11501-11509.
- (2011). Emergent membrane-affecting properties of BSA-gold nanoparticle constructs. Nanoscale. 1788-1797.
- (2011). Deconstructing honeybee vitellogenin: novel 40 kDa fragment assigned to its N terminus. Journal of Experimental Biology. 582-592.
- (2011). Benchmarking Different BAMLET-like Preparations with Resepct to Tryptophan Exposure, Interfacial Activity, and Effect on Cell Viability. Bioanalysis & Biomedicine. 5 sider.
- (2010). HAMLET interacts with lipid membranes and perturbs their structure and integrity. PLOS ONE. 10 sider.
- (2010). Adsorption and bioactivity of tyrosine hydroxylase on gold surfaces and nanoparticles. Protein & Peptide Letters. 1376-1382.
- (2009). Three-way interaction between 14-3-3 proteins, the N-terminal region of tyrosine hydroxylase and negatively charged membranes. Journal of Biological Chemistry. 32758-32769.
- (2009). Same System-Different Results: The Importance of Protein. Introduction Protocols in Langmuir-Monolayer Studies of Lipid-Protein Interactions. Analytical Chemistry. 3042-3050.
- (2009). Linking new paradigms in protein chemistry to reversible membrane-protein interactions. Current Protein & Peptide Science. 339-359.
- (2009). Exploring the Membrane Binding Capacity and Mechanism of 14-3-3γ.
- (2009). Amino acid contacts in proteins adapted to different temperatures: hydrophobic interactions and surface charges play a key role. Extremophiles. 11-20.
- (2008). Large-scale modulation of thermodynamic protein folding barriers linked to electrostatics. Proceedings of the National Academy of Sciences of the United States of America. 8625-8630.
- (2008). Amino acid contacts in proteins adapted to different temperatures: hydrophobic interactions and surface charges play a key role. Extremophiles.
- (2007). Structure-dependent relationships between growth temperature of prokaryotes and the amino acid frequency in their proteins. Extremophiles. 585-596.
- (2007). Adsorption Behavior of Acidic and Basic Proteins onto Citrate-Coated Au Surfaces Correlated to Their Native Fold, Stability, and pI. Journal of Physical Chemistry B.
- (2005). α-Lactalbumin binding and membrane integrity – effect of charge and degree of unsaturation of glycerophospholipids. Biochimica et Biophysica Acta - Biomembranes. 11-20.
- (2005). alpha-Lactalbumin binding and membrane integrity--effect of charge and degree of unsaturation of glycerophospholipids. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 11-20.
- (2005). Structure and dynamics of the peripheral protein Lactalbumin in relation to its membrane binding capability.
- (2005). Conformational flexibility of alpha-lactalbumin related to its membrane binding capacity. Journal of Molecular Biology (JMB). 1072-1086.
- (2003). The interaction of peripheral proteins and membranes studied with alpha-lactalbumin and phospholipid bilayers of various compositions. Journal of Biological Chemistry. 21790-21797.
- (2003). Direct and indirect NMR techniques applied on alpha-lactalbumin bound to different membrane-mimicking systems.
- (2002). The membrane bound conformation of alpha-lactalbumin studied by NMR.
- (2002). The Membrane-bound Conformation of a-Lactalbumin Studied by NMR-monitored 1H Exchange. Journal of Molecular Biology (JMB). 99-110.
- (2002). Studying the interaction between 14-3-3 proteins and tryptophan hydroxylase using 3D-modelling and NMR spectroscopy.
- (2002). Molten globule state of BLA bound to SDS micelles studied by NMR spectroscopy.
- (2002). Elucidating the membrane bound conformations of -lactalbumin in different lipid environments by CD, multidimensional NMR spectroscopy and fluorescence.
- (2002). Detaljer i utilgjengelig systemer membran-protein vekselvirkninger. NBS-nytt. 16-19.
- (2000). The membrane bound conformation of bovine alpha-lactalbumin studied by NMR-monitored 1H-exchange.
- (2000). Conformation of alpha-lactalbumin bound to model membranes studied by NMR-monitored hydrogen exchange.
2014:The membrane as a catalyst of damaging protein misfolding events (Research Council of Norway grant #240063)
2013: The Norwegian NMR Platform (Research Council of Norway Infrastructure grant 226244 / F50, with Finn Achmann, Frode Ride, Willy Nerdal).
2009: Interfaces as folding templates for polypetides (With associate professor Wilhelm Glomm)
2008: From details to drugs – a thorough structural and dynamic analysis of 14-3-3, tyrosine hydroxylase and membranes (Lie and Jensens fund/Norwegian Cancer Society, grant #58240001, with Professor Aurora Martínez)
2007: Dissecting molecular properties of honey bee vitellogenin (Research Council of Norway, grant #185306, with Professor Gro Vang Amdam)
2006: Linking new paradigms in protein chemistry to membrane-protein interaction, apoptosis and signalling (Norwegian Cancer Society, grant #06109/01, with Professor Aurora Martínez)
2002: Structural characterization of protein folding variants that induce apoptosis in tumor cells (Research Council of Norway, grant #149117, with Professor Aurora Martínez)
Active members
Martin Jakubec, PhD Student 2015-2018
Maxim Bril'kov, PhD Student 2014-2018
Espen Bariås, PhD Student 2017-2021
Morten Andreas Govasli Larsen, PhD Student 2015-2018 (co-supervised with Pål Puntervoll)
Vinnit Georg, Master Student 2017-2018 (co-supervised with Jarl Underhaug)
Alumni
Samuel Furse, Post Doc, 2015-2017
Lene Reed Hjorteset, Master Student 2015-2016
Øyvind Strømland, PhD Student 2012-2016
Hanzhen Wen, PhD Student 2010-2014
Ørjan Handegård, Master Student 2015-2016
Christophe Louis Balin, Master Student 2015-2016
Øyvind Ødegård, Master Student 2014-2015
Morten Andreas Govasli Larsen, Master Student 2013-2014
Helene Sandnes, Master Student 2012-2013
Ida Marie Lundgren, Master Student 2010-2011
Project Students
Martin Skarbøvik Berge (2021), Kristine Ovidia Rostad (2021, Charlotte Bekkhus (2020), Susanne Velde (2020), Marte Nesse (2019), Amanda Fond (2019), Vilde Bringsjord (2018), Vinnit Georg (2017), Ørjan Handegård (2015), Dina Grønseth (2014), Nhi Nguyen (2011), Katharina Leopold (2011)