Lipids and proteins -- their mutual influence and role in neurodegeneration and ageing.

Interested in a glimpse of one of my research projects? See this video of an invited talk where we use lipid nanodiscs to explore blind spots in the interaction between the Parkinson's Disease related protein alpha-synuclein and the lipid bilayer.

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. One of the main questions asked is whether some lipids or states of the membrane can cause certain proteins to misform, and how these misformed proteins can further affect the integritey of the cell and especially its metabolism. 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 we 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 age-realted diseases such as Parkinson's, Alzheimer's.  Findings so far indicate that cells and tissues change their lipid composition to a large extent throughout their life-time and disease state. The lipid mixes are so different that that the physical properties of the membrane changes significantly, leading to possible feedback effects on proteins associated with membranes or involved in lipid handling. In vitro, we find that different lipid mixes affect the aggregation-rates of model peptide systems.

We use zebrafish and human brain tissue to conduct neurolipidomics related to ageing and neurodegenerative diseases. Using biophysics, computer modelling and structural biology, we will investigate whether certain lipids and membrane associated proteins, such as phosphoinositides and so-called scaffold proteins, act as moderators of misfolding that can help explain how neurodegenerative diseases start and propagate. The biophysics and structural biology of this is being investigated, with a focus on “invisible protein states”, i.e., states that are not detectable by normal means. We also wish to know where in a cell misfolded protein accumulates, and whether this localization can be linked to lipid metabolism, thereby establishing a link between misfolding and lipidome. 

I also have a number of exciting collaborations. In a recent and very interesting work with Bodil Holst, we explored the lipid-related anti-icing adaptation of polar bear fur. I also work with the structural biology of honey bees in collaboration with Gro Amdam, and have investigated the structural biology and biophysics of Chromatine Regulation.

Courses taught

MOL310 - Structural Molecular Biology

MOL210 -  Lipid Biochemistry (with A. Lewis)

MOL200 - Metabolism: Reactions, Regulations and Compartmentalization (with Fergal O'Farrell and many others)

MOL270 - Bioethics (With Anders Goksøyr, Gyri Haugland and many others)

MOL220 - Techniques, model systems and current research topics in molecular biology

Supervision

By 2025, I have supervised 5 PhD students to completion as main supervisor, as well as 13 master students and 14 project students. I have also co supervised 6 PhD-students and mentored two post-docs. I have been responsible for MOL399, the Master degree at MOL since 2017, with a gap year in 2024-2025.

Discontinued courses:

MOL320 - Advanced Biophysical Techniques
 

Minor contributions:

2015: MBV 9520 (2x45 min lecture in protein dynamics, national-level Biostruct-course)

2014: MOL950 (a practical NMR module, national-level Biostruct-course)

2011-13: Lecture in BMED325 -  Nanobiochemistry

2012: Lecture in Atomic Force Microscopy (national-level Biostruct-course)

2007-11: Guest lectures and leading discussions in BMED310 - Philosophy of Science

1998-2001: Statistics (SOK33B) and Inorganic chemistry

2018

• Øyvind Halskau (2018). Contrasting cellular lipid states using quantitative 31P NMR and LC MS/MS. (external link)
• Behdad Delavari; Fatemeh Mamashli; Bahareh Bigdeli et al. (2018). A biophysical study on the mechanism of interactions of DOX or PTX with α-lactalbumin as a delivery carrier. (external link)
• Maxim Brilkov; Olena Dobrovolska; Rein Aasland et al. (2018). CW-domain of ASHH2 methyltransferase: structural basis of ligand binding and specificity. (external link)
• Martin Jakubec; Øyvind Halskau; Astrid Elisabeth Mork-Jansson (2018). A novel exosome-like nanocarrier for treatment of refractory epilepsy. (external link)
• Martin Jakubec; Øyvind Halskau; Damir Janigro et al. (2018). A novel exosome-like nanocarrier for treatment of refractory epilepsy. (external link)
• Olena Dobrovolska; Maxim Brilkov; Øyvind Ødegård‑Fougner et al. (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. (external link)
• Øyvind Halskau (2018). Proteiner og nevrodegenerative sykdommer. (external link)
• Martin Jakubec; Georg Vinnit; Morten Andreas Govasli Larsen et al. (2018). Alpha-synuclein oligomerization in the presence of the cholesterol and glycerophosphoglycerol. (external link)
• Martin Jakubec; Øyvind Halskau; Damir Janigro et al. (2018). A novel exosome-like nanocarrier for treatment of refractory epilepsy. (external link)

2002

• Øyvind Halskau; Jarl Underhaug; Nils Å. Frøystein et al. (2002). Molten globule state of BLA bound to SDS micelles studied by NMR spectroscopy. (external link)
• Øyvind Halskau; Knut Teigen; Rune Kleppe et al. (2002). Studying the interaction between 14-3-3 proteins and tryptophan hydroxylase using 3D-modelling and NMR spectroscopy. (external link)
• Øyvind Halskau; Nils Å. Frøystein; Arturo Muga et al. (2002). The Membrane-bound Conformation of a-Lactalbumin Studied by NMR-monitored 1H Exchange. (external link)
• Øyvind Halskau; Armelle, V. Agasøster; Aurora Martinez et al. (2002). Elucidating the membrane bound conformations of -lactalbumin in different lipid environments by CD, multidimensional NMR spectroscopy and fluorescence. (external link)
• Øyvind Halskau; Nils Å. Frøystein; Matthias Thorolfsson et al. (2002). The membrane bound conformation of alpha-lactalbumin studied by NMR. (external link)
• Øyvind Halskau; Nils Å. Frøystein; Aurora Martinez (2002). Detaljer i utilgjengelig systemer – membran-protein vekselvirkninger. (external link)

2019

• Martin Jakubec; Øyvind Halskau (2019). Neuronal cell lipidomics and role of cholesterol in α-synuclein binding and aggregation. (external link)
• Martin Jakubec; Espen Bariås; Fedor Kryuchkov et al. (2019). Fast and quantitative phospholipidomic analysis of SH-SY5Y neuroblastoma cell cultures using LC-MS/MS and 31P NMR. (external link)
• Øyvind Halskau (2019). Misfolding i neurodegenerative sykdommer. (external link)
• Øyvind Halskau (2019). Neurodegenerative sykdommer -- proteinkrøll gir hjernekrøll. (external link)
• Morten Andreas Govasli Larsen; Pål Puntervoll; Øyvind Halskau (2019). From potent toxin to vaccine toxoid: Engineering the enterotoxigenic Escherichia coli heat-stable toxin into a subunit vaccine component. (external link)

2016

• Samuel Robert Furse; Martin Jakubec; Michelle Victoria Hauge et al. (2016). Why is HAMLET more toxic to dividing cells?. (external link)
• Øyvind Halskau (2016). Reversible protein membrane interactions by mobile peptides.. (external link)
• Lene Hjortset; Øyvind Strømland; Ørjan Handegård et al. (2016). Characterization of protein-fatty acid complexe. (external link)
• Øyvind Halskau (2016). Relevance of the protein, fatty acid and lipid component in early stages of HAMLET induced cell death. (external link)
• Martin Jakubec; Øyvind Strømland; Samuel Robert Furse et al. (2016). Detection of misfolded protein aggregates from a clinical perspective. (external link)
• Reed Lene Hjortset; Øyvind Halskau (2016). Molecular Characteristics of Peptide-Fatty Acid Complex Relevant for Tumoricidal HAMLET. (external link)
• Øyvind Strømland; Martin Jakubec; Samuel Robert Furse et al. (2016). Detection of Misfolded Protein Aggregates from a Clinical Perspective. (external link)
• Øyvind Halskau (2016). The protein, fatty acid and lipid components in early stages of PFA/HAMLET-induced cell death. (external link)
• Christophe Louis Balin; Øyvind Halskau (2016). Expression and purification of misfolding peptides from E. coli for spectroscopic characterization. (external link)

2017

• Samuel Robert Furse; Martin Jakubec; Frode Rise et al. (2017). Does the lipid fractio of Listeria innocua change as a function of the cell cycle?. (external link)
• Samuel Robert Furse; Martin Jakubec; Frode Rise et al. (2017). Evidence that Listeria innocua modulates its membrane's stored curvature elastic stress, but not fluidity, through the cell cycle. (external link)
• Øyvind Strømland; Ørjan Sele Handegård; Morten Andreas Govasli Larsen et al. (2017). Peptides derived from α-lactalbumin membrane binding helices oligomerize in presence of lipids and disrupt bilayers. (external link)
• Øyvind Halskau (2017). Lecture on the Nobel Prize of Chemistry 2017 (Cryo-EM). (external link)
• Øyvind Strømland; Ørjan S. Handegård; Morten Andreas Govasli Larsen et al. (2017). Spectroscopic and AFM characterization of polypeptide-surface interactions: Controls and lipid quantitative analyses. (external link)

2013

• Hanzhen Wen; Wilhelm Glomm; Øyvind Halskau (2013). Cytotoxicity of bovine alpha-lactalbumin: Oleic acid complexes correlates with the disruption of lipid membranes. (external link)
• Helene Heitmann Sandnes; Øyvind Halskau (2013). CREATING BAMLET USING ALPs AND INVESTIGATING THEIR EFFECT ON DIFFERENTIATED AND NONDIFFERENTIATED HUMAN BREAST CANCER CELLS. (external link)
• Heli Havukainen; Daniel Münch; Anne Baumann et al. (2013). Vitellogenin recognizes cell damage through membrane binding and shields living cells from reactive oxygen species. (external link)
• Sina Maria Lystvet; Sondre Volden; Gurvinder Singh et al. (2013). Tunable photophysical properties, conformation and function of nanosized protein–gold constructs. (external link)
• Sina Maria Lystvet; Sondre Volden; Gurvinder Singh et al. (2013). Anticancer Activity from Gold-alpha-Lactalbumin Nanoconstructs?. (external link)
• Sara Marie Øie Solbak; Tove Ragna Reksten; Friedrich Hahn et al. (2013). HIV-1 p6 - a structured to flexible multifunctional membrane-interacting protein. (external link)

2023

• Espen Bariås; Martin Jakubec; Elise Førsund et al. (2023). Contrasting the phospholipid profiles of two neoplastic cell lines reveal a high PC:PE ratio for SH-SY5Y cells relative to A431 cells. (external link)
• Mateu Montserrat Canals; Kilian Schnelle; Vilde Leipart et al. (2023). The high-resolution cryo-EM structure of vitellogenin from the hemolymph of the honey bee. (external link)
• Nicolai Etwin Alsaker; Willy Nerdal; Bengt Erik Haug et al. (2023). Phospholipid membrane interactions of model peptides and depth of insertion investigated via solid-state NMR. (external link)

2011

• Sina Maria Lystvet; Sondre Volden; Masahiro Yasuda et al. (2011). Emergent membrane-affecting properties of BSA-gold nanoparticle constructs. (external link)
• Wilhelm Glomm; Sondre Volden; Marit-Helen Ese et al. (2011). Interactions of α-Lactalbumin and Cytochrome с with Langmuir Monolayers of Glycerophospholipids. (external link)
• Hanzhen Wen; Ida M. Rundgren; Wilhelm Glomm et al. (2011). Benchmarking Different BAMLET-like Preparations with Resepct to Tryptophan Exposure, Interfacial Activity, and Effect on Cell Viability. (external link)
• Helene Bustad Johannessen; Jarl Underhaug; Øyvind Halskau jr et al. (2011). The binding of 14-3-3 gamma to membranes studied by intrinsic fluorescence spectroscopy. (external link)
• Heli Havukainen; Øyvind Halskau jr; Lars Skjærven et al. (2011). Deconstructing honeybee vitellogenin: novel 40 kDa fragment assigned to its N terminus. (external link)
• Sina Maria Lystvet; Sondre Volden; Øyvind Halskau jr et al. (2011). Immobilizaton onto gold nanoparticles alters α-lactalbumin interaction with pure and mixed phospholipid monolayers. (external link)
• Sondre Volden; Masahiro Yasuda; Øyvind Halskau jr et al. (2011). Mechanism for tunable protein deposition onto charged monodisperse polymer nanoparticles. (external link)
• Heli Havukainen; Øyvind Halskau jr; Gro Vang Amdam (2011). Social pleiotropy and evolution of honey bee vitellogenin. (external link)
• Sina Maria Lystvet; Sondre Volden; Masahiro Yasuda et al. (2011). Teaching old proteins new tricks. (external link)

2005

• Øyvind Halskau; Jarl Underhaug; Nils Åge Frøystein et al. (2005). Conformational flexibility of alpha-lactalbumin related to its membrane binding capacity. (external link)
• Ingunn Rødland; Øyvind Halskau; Aurora Martinez et al. (2005). α-Lactalbumin binding and membrane integrity – effect of charge and degree of unsaturation of glycerophospholipids. (external link)
• Øyvind Halskau jr (2005). Structure and dynamics of the peripheral protein Lactalbumin in relation to its membrane binding capability. (external link)
• Ingunn Rødland; Øyvind Halskau; Aurora Martinez et al. (2005). alpha-Lactalbumin binding and membrane integrity--effect of charge and degree of unsaturation of glycerophospholipids. (external link)

2020

• Øyvind Halskau (2020). Conformational selection in histone binding – when being rigid fails. (external link)
• Espen Bariås; Martin Jakubec; Øyvind Halskau (2020). Lipiders rolle i nevrodegenerative sykdommer. (external link)
• Elise Førsund; Øyvind Halskau (2020). Senescence-Related Changes to the Lipid Composition of SH-SY5Y Cells with Implications for α-Synuclein Misfolding. (external link)
• Olena Dobrovolska; Maxim Brilkov; Noëlly Madeleine et al. (2020). The Arabidopsis (ASHH2) CW domain binds monomethylated K4 of the histone H3 tail through conformational selection. (external link)
• Martin Jakubec; Jodi Maple-Grødem; Saleha Akbari et al. (2020). Plasma-derived exosome-like vesicles are enriched in lyso-phospholipids and pass the blood-brain barrier. (external link)
• Martin Jakubec; Christian Totland; Frode Rise et al. (2020). Bioactive metabolites of marine origin have unusual effects on model membrane systems. (external link)
• Martin Jakubec; Espen Bariås; Samuel Robert Furse et al. (2020). Cholesterol-containing lipid nanodiscs promote an α-synuclein binding mode that accelerates oligomerization. (external link)
• Trond-André Kråkenes; Fredrik Gullaksen Johannessen; Martin Jakubec et al. (2020). Phosphorylated TH hinges with vesicular membrane proteins for axonal transport. (external link)
• Mette Ovesen; Øyvind Halskau (2020). The Attenuating Effects of 14-3-3eta in Parkinson’s Disease-Related alpha-Synuclein Aggregation. (external link)

2012

• Anne Baumann; Anja Underhaug Gjerde; Ming Ying et al. (2012). HAMLET forms annular oligomers when deposited with phoshpolipid monolayers. (external link)
• Svein Isungset Støve; Angele Abboud; Cédric Grauffel et al. (2012). An x-linked infantile lethal disorder caused by N-terminal acetyltransferase deficiency. (external link)
• Heli Havukainen; Jarl Underhaug; Florian Wolschin et al. (2012). A vitellogenin polyserine cleavage site: highly disordered conformation protected from proteolysis by phosphorylation. (external link)
• Sina Maria Lystvet; Sondre Volden; Øyvind Halskau jr et al. (2012). Interactions between BSA-gold nanoparticle constructs and a phospholipid monolayer. (external link)
• Sondre Volden; Sina Maria Lystvet; Øyvind Halskau jr et al. (2012). Generally applicable procedure for in situ formation of fluorescent protein-gold nanoconstructs. (external link)
• Anne-Sophie Schillinger; Cédric Grauffel; Øyvind Halskau et al. (2012). PR3 Interacts Directly to Lipid Bilayers: Evidence from MD Simulations and SPR Experiments. (external link)
• Helene J. Bustad; Lars Skjærven; Ming Ying et al. (2012). The peripheral binding of 14-3-3gamma to membranes involves isoform-specific histidine residues. (external link)
• Anne-Sophie Schillinger; Cédric Grauffel; Øyvind Halskau et al. (2012). PR3 Interacts Directly to Lipid Bilayers: Evidence from MD Simulations and SPR Experiments. (external link)

2021

• Olena Dobrovolska; Øyvind Strømland; Ørjan Sele Handegård et al. (2021). Investigating the Disordered and Membrane-Active Peptide A-Cage-C Using Conformational Ensembles. (external link)
• Vilde Leipart; Mateu Montserrat Canals; Eva Mariana de Sousa Cunha et al. (2021). Structure prediction of honey bee vitellogenin: a multi-domain protein important for insect immunity. (external link)
• Milada Vitova; Vojtech Lanta; Maria Cizkova et al. (2021). The biosynthesis of phospholipids is linked to the cell cycle in a model eukaryote. (external link)

2007

• Wilhelm R Glomm; Øyvind Halskau jr; Øyvind Halskau, Jr. et al. (2007). Adsorption Behavior of Acidic and Basic Proteins onto Citrate-Coated Au Surfaces Correlated to Their Native Fold, Stability, and pI. (external link)
• G Saelensminde; Gisle Sælensminde; O Halskau et al. (2007). Structure-dependent relationships between growth temperature of prokaryotes and the amino acid frequency in their proteins. (external link)

2015

• Hanzhen Wen; Øyvind Strømland; Øyvind Halskau (2015). α-lactalbumin: oleic acid complex spontaneously delivers oleic acid to artificial and erythrocyte membranes. (external link)

2003

• Armelle, V. Agasøster; Øyvind Halskau; Edvin Fuglebakk et al. (2003). The interaction of peripheral proteins and membranes studied with alpha-lactalbumin and phospholipid bilayers of various compositions. (external link)
• Øyvind Halskau; Jarl Underhaug; Nils Å. Frøystein et al. (2003). Direct and indirect NMR techniques applied on alpha-lactalbumin bound to different membrane-mimicking systems. (external link)

2009

• Helene Bustad Johannessen; Øyvind Halskau jr; Aurora Martinez (2009). Exploring the Membrane Binding Capacity and Mechanism of 14-3-3γ. (external link)
• Wilhelm Robert Glomm; Sondre Volden; O Halskau et al. (2009). Same System-Different Results: The Importance of Protein. Introduction Protocols in Langmuir-Monolayer Studies of Lipid-Protein Interactions. (external link)
• Gisle Sælensminde; Øyvind Halskau jr; Inge Jonassen (2009). Amino acid contacts in proteins adapted to different temperatures: hydrophobic interactions and surface charges play a key role. (external link)
• Øyvind Halskau jr; Arturo Muga; Aurora Martinez (2009). Linking new paradigms in protein chemistry to reversible membrane-protein interactions. (external link)
• Øyvind Halskau jr; Ming Ying; Anne Baumann et al. (2009). Three-way interaction between 14-3-3 proteins, the N-terminal region of tyrosine hydroxylase and negatively charged membranes. (external link)

2014

• Anne-Sophie Schillinger; Cédric Grauffel; Hanif Muhammad Khan et al. (2014). Two homologous neutrophil serine proteases bind to POPC vesicles with different affinities: When aromatic amino acids matter. (external link)
• Åge Aleksander Skjevik; Mauro Mileni; Anne Baumann et al. (2014). The N-terminal sequence of tyrosine hydroxylase is a conformationally versatile motif that binds 14-3-3 proteins and membranes. (external link)

2024

• Birta Ravdna Alexandersen Sarre; Olena Dobrovolska; Patrik Lundström et al. (2024). Structural dynamics of human deoxyuridine 5’-triphosphate nucleotidohydrolase (dUTPase). (external link)
• Nicolai Etwin Alsaker; Øyvind Halskau; Bengt Erik Haug et al. (2024). Phospholipid Membrane Interactions of Model Ac-WL-X-LL-OH Peptides Investigated by Solid-State Nuclear Magnetic Resonance. (external link)

2010

• Ann-Kristin Mossberg; Maja Puchades; Øyvind Halskau jr et al. (2010). HAMLET interacts with lipid membranes and perturbs their structure and integrity. (external link)
• Øyvind Halskau jr; Sondre Volden; Ana C Calvo et al. (2010). Adsorption and bioactivity of tyrosine hydroxylase on gold surfaces and nanoparticles. (external link)

2022

• Vilde Leipart; Øyvind Halskau; Gro Vang Amdam (2022). How Honey Bee Vitellogenin Holds Lipid Cargo: A Role for the C-Terminal. (external link)
• Vilde Leipart; Øyvind Enger; Diana Cornelia Turcu et al. (2022). Resolving the zinc binding capacity of honey bee vitellogenin and locating its putative binding sites. (external link)
• Maxim Bril'kov; Olena Dobrovolska; Øyvind Ødegård-Fougner et al. (2022). Binding Specificity of ASHH2 CW Domain Toward H3K4me1 Ligand Is Coupled to Its Structural Stability Through Its α1-Helix. (external link)

2025

• Mateu Montserrat Canals; Kilian Schnelle; Vilde Leipart et al. (2025). Cryo-EM structure of native honey bee vitellogenin. (external link)
• Julian Carolan; Martin Jakubec; Neubi F. Xavier et al. (2025). Anti-icing properties of polar bear fur. (external link)

2000

• Øyvind Halskau; N.Å. Frøystein; Aurora Martinez et al. (2000). Conformation of alpha-lactalbumin bound to model membranes studied by NMR-monitored hydrogen exchange. (external link)
• Øyvind Halskau (2000). The membrane bound conformation of bovine alpha-lactalbumin studied by NMR-monitored 1H-exchange. (external link)

2008

• Gisle Sælensminde; Øyvind Halskau jr; Inge Jonassen (2008). Amino acid contacts in proteins adapted to different temperatures: hydrophobic interactions and surface charges play a key role. (external link)
• Øyvind Halskau jr; Raul Perez-Jimenez; Beatriz Ibarra-Molero et al. (2008). Large-scale modulation of thermodynamic protein folding barriers linked to electrostatics. (external link)

See a complete overview of publications in Cristin.

Here is my academic production in:

PubMed

Google Scholar

Web of Science

Below is also my CRIStin publication list. 

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)