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  • E-mailOyvind.Halskau@uib.no
  • Phone+47 55 58 45 63
  • Visitor Address
    Thormøhlensgt. 53 A/B
    Room 
    524C2
  • Postal Address
    Postboks 7803
    5020 Bergen

Lipids as catalysts of protein misfolding

The unit of life is the cell. Its outer border is the cell membrane, a thin sheet just a few nanometers thick. This is not a solid barrier, but rather a semi-fluid oil-like affair. It consists of lipids, molecules similar to fats or oils and proteins. There are also chains of sugar molecules linked to it. The cell membrane allows some molecules to pass through it, but is impassable to others. Many of both the protein, lipid and sugar molecules of the cell membrane are well-understood in terms individual behavior. But in the complex and constantly changing environment of the membrane it has remained a challenge to understand how each component may affect each other. And understanding this interplay is critical for understanding the molecular foundation of the cell. This project intends to examine how lipids affect proteins and how proteins affect the integrity of the lipid assembly that gives the cell membrane its integrity as a barrier. One of the main questions asked is whether some lipids or states of the membrane can cause certain proteins to misform. Proteins normally need to twist their shape into a specific structure, or fold, to gain their function. If this process, which is usually spontaneous, is disturbed, they can form damaging states instead. This is normally referred to as protein misfolding, and the project asks whether some lipids can prompt certain membrane-associated proteins to misfold at a quicker pace than they normally would. Such misfolding events are implicated in many diseases, including Parkinson's, Alzheimer's and Diabetes II, as well as prionic diseases. If the scientific question is well posed and the project manages to pursue it with appropriate techniques it is possible that one might gain new and detailed insight into disease mechanisms. This could in time lead to better prevention or treatments. Our preliminary findings indicate that cells modulate their lipid composition to a large extent throughout their life-time. The lipid mixes are so different that that the physical properties of the membrane changes significantly. We also find that different lipid mixes affect the aggregation-rates of model peptide systems.

I also work with the structural biology and biophysics of Chromatine Regulation.

Courses taught

MOL310 - Structural Molecular Biology

MOL320 - Advanced Biophysical Techniques

MOL210 -  Lipid Biochemistry (with A. Lewis)

Minor contributions:

2015:

2014:

2011-13:

2012:

2007-11:

1998-2001:

MBV 9520 (2x45 min lecture in protein dynamics, national-level Biostruct-course)

MOL950 (a practical NMR module, national-level Biostruct-course)

Lecture in BMED325Nanobiochemistry

Lecture in Atomic Force Microscopy (national-level Biostruct-course)

Guest lectures and leading discussions in BMED310 - Philosophy of Science

Statistics (SOK33B) and Inorganic chemistry

Here is my academic production in:

PubMed

Google Scholar

Web of Science

Below is also my CRIStin publication list. 

  • Show author(s) 2020. The Attenuating Effects of 14-3-3eta in Parkinson’s Disease-Related alpha-Synuclein Aggregation.
  • Show author(s) 2020. The Arabidopsis (ASHH2) CW domain binds monomethylated K4 of the histone H3 tail through conformational selection. The FEBS Journal. 4458-4480.
  • Show author(s) 2020. Senescence-Related Changes to the Lipid Composition of SH-SY5Y Cells with Implications for α-Synuclein Misfolding.
  • Show author(s) 2020. Plasma-derived exosome-like vesicles are enriched in lyso-phospholipids and pass the blood-brain barrier. PLOS ONE. 1-15.
  • Show author(s) 2020. Lipiders rolle i nevrodegenerative sykdommer. NBS-nytt.
  • Show author(s) 2020. Conformational selection in histone binding – when being rigid fails.
  • Show author(s) 2020. Cholesterol-containing lipid nanodiscs promote an α-synuclein binding mode that accelerates oligomerization. The FEBS Journal.
  • Show author(s) 2020. Bioactive metabolites of marine origin have unusual effects on model membrane systems. Marine Drugs. 1-11.
  • Show author(s) 2019. Neuronal cell lipidomics and role of cholesterol in α-synuclein binding and aggregation.
  • Show author(s) 2019. Neurodegenerative sykdommer -- proteinkrøll gir hjernekrøll.
  • Show author(s) 2019. Misfolding i neurodegenerative sykdommer.
  • Show author(s) 2019. From potent toxin to vaccine toxoid: Engineering the enterotoxigenic Escherichia coli heat-stable toxin into a subunit vaccine component.
  • Show author(s) 2019. Fast and quantitative phospholipidomic analysis of SH-SY5Y neuroblastoma cell cultures using LC-MS/MS and 31P NMR. ACS Omega. 21596-21603.
  • Show author(s) 2018. Proteiner og nevrodegenerative sykdommer.
  • Show author(s) 2018. Contrasting cellular lipid states using quantitative 31P NMR and LC MS/MS .
  • Show author(s) 2018. CW-domain of ASHH2 methyltransferase: structural basis of ligand binding and specificity.
  • Show author(s) 2018. Alpha-synuclein oligomerization in the presence of the cholesterol and glycerophosphoglycerol.
  • Show author(s) 2018. A novel exosome-like nanocarrier for treatment of refractory epilepsy .
  • Show author(s) 2018. A novel exosome-like nanocarrier for treatment of refractory epilepsy .
  • Show author(s) 2018. A novel exosome-like nanocarrier for treatment of refractory epilepsy .
  • Show author(s) 2018. A biophysical study on the mechanism of interactions of DOX or PTX with α-lactalbumin as a delivery carrier. Scientific Reports. 1-21.
  • Show author(s) 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.
  • Show author(s) 2017. Spectroscopic and AFM characterization of polypeptide-surface interactions: Controls and lipid quantitative analyses. Data in Brief. 113-122.
  • Show author(s) 2017. Peptides derived from α-lactalbumin membrane binding helices oligomerize in presence of lipids and disrupt bilayers. Biochimica et Biophysica Acta - Biomembranes. 1029-1039.
  • Show author(s) 2017. Lecture on the Nobel Prize of Chemistry 2017 (Cryo-EM).
  • Show author(s) 2017. Evidence that Listeria innocua modulates its membrane's stored curvature elastic stress, but not fluidity, through the cell cycle. Scientific Reports. 1-11.
  • Show author(s) 2017. Does the lipid fractio of Listeria innocua change as a function of the cell cycle?
  • Show author(s) 2016. Why is HAMLET more toxic to dividing cells?
  • Show author(s) 2016. The protein, fatty acid and lipid components in early stages of PFA/HAMLET-induced cell death.
  • Show author(s) 2016. Reversible protein membrane interactions by mobile peptides.
  • Show author(s) 2016. Relevance of the protein, fatty acid and lipid component in early stages of HAMLET induced cell death.
  • Show author(s) 2016. Molecular Characteristics of Peptide-Fatty Acid Complex Relevant for Tumoricidal HAMLET.
  • Show author(s) 2016. Expression and purification of misfolding peptides from E. coli for spectroscopic characterization.
  • Show author(s) 2016. Detection of misfolded protein aggregates from a clinical perspective. Journal of Clinical and Translational Research. 11-26.
  • Show author(s) 2016. Detection of Misfolded Protein Aggregates from a Clinical Perspective. Journal of Clinical and Translational Research. 11-26.
  • Show author(s) 2016. Characterization of protein-fatty acid complexe.
  • Show author(s) 2015. α-lactalbumin: oleic acid complex spontaneously delivers oleic acid to artificial and erythrocyte membranes. Journal of Molecular Biology (JMB). 3177-3187.
  • Show author(s) 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.
  • Show author(s) 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.
  • Show author(s) 2013. Vitellogenin recognizes cell damage through membrane binding and shields living cells from reactive oxygen species. Journal of Biological Chemistry. 28369-28381.
  • Show author(s) 2013. Tunable photophysical properties, conformation and function of nanosized protein–gold constructs. RSC Advances. 482-495.
  • Show author(s) 2013. HIV-1 p6 - a structured to flexible multifunctional membrane-interacting protein. Biochimica et Biophysica Acta - Biomembranes. 816-823.
  • Show author(s) 2013. Cytotoxicity of bovine alpha-lactalbumin: Oleic acid complexes correlates with the disruption of lipid membranes. Biochimica et Biophysica Acta - Biomembranes. 2691-2699.
  • Show author(s) 2013. CREATING BAMLET USING ALPs AND INVESTIGATING THEIR EFFECT ON DIFFERENTIATED AND NONDIFFERENTIATED HUMAN BREAST CANCER CELLS.
  • Show author(s) 2013. Anticancer Activity from Gold-alpha-Lactalbumin Nanoconstructs? Journal of Physical Chemistry C. 2230-2238.
  • Show author(s) 2012. The peripheral binding of 14-3-3gamma to membranes involves isoform-specific histidine residues. PLOS ONE.
  • Show author(s) 2012. PR3 Interacts Directly to Lipid Bilayers: Evidence from MD Simulations and SPR Experiments. Biophysical Journal. 497A-497A.
  • Show author(s) 2012. PR3 Interacts Directly to Lipid Bilayers: Evidence from MD Simulations and SPR Experiments.
  • Show author(s) 2012. Interactions between BSA-gold nanoparticle constructs and a phospholipid monolayer.
  • Show author(s) 2012. HAMLET forms annular oligomers when deposited with phoshpolipid monolayers. Journal of Molecular Biology (JMB). 90-102.
  • Show author(s) 2012. Generally applicable procedure for in situ formation of fluorescent protein-gold nanoconstructs. RSC Advances. 11704-11711.
  • Show author(s) 2012. An x-linked infantile lethal disorder caused by N-terminal acetyltransferase deficiency.
  • Show author(s) 2012. A vitellogenin polyserine cleavage site: highly disordered conformation protected from proteolysis by phosphorylation. Journal of Experimental Biology. 1837-1846.
  • Show author(s) 2011. The binding of 14-3-3 gamma to membranes studied by intrinsic fluorescence spectroscopy. FEBS Letters. 1163-1168.
  • Show author(s) 2011. Teaching old proteins new tricks.
  • Show author(s) 2011. Social pleiotropy and evolution of honey bee vitellogenin. Molecular Ecology. 5111-5113.
  • Show author(s) 2011. Mechanism for tunable protein deposition onto charged monodisperse polymer nanoparticles.
  • Show author(s) 2011. Interactions of α-Lactalbumin and Cytochrome с with Langmuir Monolayers of Glycerophospholipids. Journal of Dispersion Science and Technology. 150-158.
  • Show author(s) 2011. Immobilizaton onto gold nanoparticles alters α-lactalbumin interaction with pure and mixed phospholipid monolayers. Soft Matter. 11501-11509.
  • Show author(s) 2011. Emergent membrane-affecting properties of BSA-gold nanoparticle constructs. Nanoscale. 1788-1797.
  • Show author(s) 2011. Deconstructing honeybee vitellogenin: novel 40 kDa fragment assigned to its N terminus. Journal of Experimental Biology. 582-592.
  • Show author(s) 2011. Benchmarking Different BAMLET-like Preparations with Resepct to Tryptophan Exposure, Interfacial Activity, and Effect on Cell Viability. Bioanalysis & Biomedicine. 5 pages.
  • Show author(s) 2010. HAMLET interacts with lipid membranes and perturbs their structure and integrity. PLOS ONE. 10 pages.
  • Show author(s) 2010. Adsorption and bioactivity of tyrosine hydroxylase on gold surfaces and nanoparticles. Protein & Peptide Letters. 1376-1382.
  • Show author(s) 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.
  • Show author(s) 2009. Same System-Different Results: The Importance of Protein. Introduction Protocols in Langmuir-Monolayer Studies of Lipid-Protein Interactions. Analytical Chemistry. 3042-3050.
  • Show author(s) 2009. Linking new paradigms in protein chemistry to reversible membrane-protein interactions. Current Protein & Peptide Science. 339-359.
  • Show author(s) 2009. Exploring the Membrane Binding Capacity and Mechanism of 14-3-3γ.
  • Show author(s) 2009. Amino acid contacts in proteins adapted to different temperatures: hydrophobic interactions and surface charges play a key role. Extremophiles. 11-20.
  • Show author(s) 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.
  • Show author(s) 2008. Amino acid contacts in proteins adapted to different temperatures: hydrophobic interactions and surface charges play a key role. Extremophiles.
  • Show author(s) 2007. Structure-dependent relationships between growth temperature of prokaryotes and the amino acid frequency in their proteins. Extremophiles. 585-596.
  • Show author(s) 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.
  • Show author(s) 2005. α-Lactalbumin binding and membrane integrity – effect of charge and degree of unsaturation of glycerophospholipids. Biochimica et Biophysica Acta - Biomembranes. 11-20.
  • Show author(s) 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.
  • Show author(s) 2005. Structure and dynamics of the peripheral protein Lactalbumin in relation to its membrane binding capability.
  • Show author(s) 2005. Conformational flexibility of alpha-lactalbumin related to its membrane binding capacity. Journal of Molecular Biology (JMB). 1072-1086.
  • Show author(s) 2003. The interaction of peripheral proteins and membranes studied with alpha-lactalbumin and phospholipid bilayers of various compositions. Journal of Biological Chemistry. 21790-21797.
  • Show author(s) 2003. Direct and indirect NMR techniques applied on alpha-lactalbumin bound to different membrane-mimicking systems.
  • Show author(s) 2002. The membrane bound conformation of alpha-lactalbumin studied by NMR.
  • Show author(s) 2002. The Membrane-bound Conformation of a-Lactalbumin Studied by NMR-monitored 1H Exchange. Journal of Molecular Biology (JMB). 99-110.
  • Show author(s) 2002. Studying the interaction between 14-3-3 proteins and tryptophan hydroxylase using 3D-modelling and NMR spectroscopy.
  • Show author(s) 2002. Molten globule state of BLA bound to SDS micelles studied by NMR spectroscopy.
  • Show author(s) 2002. Elucidating the membrane bound conformations of -lactalbumin in different lipid environments by CD, multidimensional NMR spectroscopy and fluorescence.
  • Show author(s) 2002. Detaljer i utilgjengelig systemer – membran-protein vekselvirkninger. NBS-nytt. 16-19.
  • Show author(s) 2000. The membrane bound conformation of bovine alpha-lactalbumin studied by NMR-monitored 1H-exchange.
  • Show author(s) 2000. Conformation of alpha-lactalbumin bound to model membranes studied by NMR-monitored hydrogen exchange.

More information in national current research information system (CRIStin)

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

Vinnit Georg (2017), Ørjan Handegård (2015), Nhi Nguyen (2011), Katharina Leopold (2011)

2014:The membrane as a catalyst of damaging protein misfolding events (Research Council of Norway grant #240063)

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)