Øyvind Halskau

Position

Professor

Affiliation

Research groups

Research

Lipids as catalysts of protein misfolding

For a fairly recent invited lecture, please see this youtube video.

 

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 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 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.

We aim to use zebrafish as model organism to conduct neurolipidomics related to ageing and (models) of neurodegenerative diseases. Using biophysics and structural biology, we will investigate whether certain lipids and membrane associated proteins, in particular phosphoinositides and so-called scaffold proteins , act as moderators of misfolding. 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. We will introduce of misfolders (in functional, misfolded and inert states) into cells to discover subcellular locations affected by misfolding, with a particular attention to functional assemblies of lipases, cholesterol and phosphoinesotides.

I also work with the structural biology and biophysics of Chromatine Regulation, as well as the structural biology of honey bees in collaboration with Gro Amdam.

Teaching

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 BMED325 -  Nanobiochemistry

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

Guest lectures and leading discussions in BMED310 - Philosophy of Science

Statistics (SOK33B) and Inorganic chemistry

Publications

Here is my academic production in:

PubMed

Google Scholar

Web of Science

Below is also my CRIStin publication list. 

2024
2023
2022
2021
2020
2019
2018
2017
2016
2015
2014
2013
2012
2011
2010
2009
2008
2007
2005
2003
2002
2000

See a complete overview of publications in Cristin.

Projects

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)

Forskningsgruppe

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)