Predicting disease genes with causal inference

Scientists are trying to figure out which genes cause diseases like heart disease and which ones don’t. This is tricky because many genes are close together on the genome and are affected by the same DNA variations. Mariyam Khan, a PhD student in the Michoel group, used an old mathematical idea from the theory of causal inference to improve a method called Mendelian randomization. This method helps scientists understand how certain factors affect health. Her new approach (in PLoS Genetics) can identify which genes are likely causing diseases, even in complicated areas of the genome. When tested on data from 600 heart surgery patients, it confirmed that some genes, like PHACTR1 and ADAMTS7, are involved in heart disease and found new genes that need more research.

November 11, 2024

Postdoc Sean Alexander Bankier – Young Scientist Award 2024

Japan Society for Human Genetics has awarded Sean Bankier, postdoctoral fellow in the Michoel Group, with the Young Scientist Award 2024. JHG Young Scientist Award recognises articles by young researchers that have made significant contribution to Journal of Human Genetics, thanks to their scientific excellence and impact in the field of human genetics.

Bankier received the award for the article “Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease“

November 4, 2024

Learning evolutionary and progression pathways over time

Many important processes in biology and medicine involve a progressive buildup of features over time. These might be, for example, the accumulation of different mutations as cancer progresses, or the evolution of bacteria to be resistant to more and more drugs. In PLoS Computational Biology, we have developed a new algorithm called HyperTraPS-CT uses data to learn the details of how these features build up over time. We demonstrate its use in learning about leukemia progression and tuberculosis drug resistance.

September 4, 2024

_{Picture: Iain Johnston}

Lipid extraction by the STARD2 lipid transfer protein

Reza Talandashti, PhD candidate in the Reuter group, used molecular dynamics simulations and free energy calculations and proposes a model for the mechanism by which STARD2 extracts choline lipids from the endoplasmic reticulum membrane. Reza’s work is published in the Journal of Physical Chemistry Letters.

August 6, 2024

Feast or famine: how sea anemones resize their bodies to survive

Unlike other animals, sea anemones grow and shrink dramatically when fed or starved. Their bodies can get over ten times bigger when they consume a lot of food, then shrink back ten times smaller again. A collaboration between the Computational Biology Unit and the Michael Sars Centre, published in Development, has revealed how these creatures manage these enormous changes in body size.

You can also read the UiB news story.

July 9, 2024

_{Picture: Alexandre Jan}

Molecular simulations shed light on lipid transfer mechanism

Lipid transfer proteins (also known as LTPs) facilitate non-vesicular lipid transport between organelle membranes and regulate various cellular processes, including signal transduction and lipid metabolism. The mechanisms by which LTPs bind to membranes and extract/release lipids from/into well-packed membranes are extremely complex. They are also extremely challenging to address with experimental set-ups. In two recently published works, we used molecular dynamics simulations to propose mechanistic models for two LTPs transferring either cholesterol (STARD 4), or ceramide (CERT/STARD11). Both models could be validated by experiments and reveal conformational changes undergone by the proteins in the process, and the active role played by the membrane in the lipid extraction and release processes. The works are published in J.Mol.Biol (doi.org/10.1016/j.jmb.2024.168572) and J.Phys.Chem.B (doi.org/10.1021/acs.jpcb.4c02398).

June 22, 2024

Universal evolution in mitochondria and chloroplasts

Mitochondria and chloroplasts power complex life. They have their own genomes, which encode vital parts of bioenergetic machinery. These genomes have become reduced over evolutionary history. Previous research from the CBU has hypothesised “universal” rules shaping these genomes. In Molecular Biology and Evolution, our new research supports this hypothesis, by showing that evolutionary reduction has occurred similarly in mitochondria and chloroplasts.

May 17, 2024

_{Picture: Iain Johnston}

_{Picture: Iain Johnston/ New Phytologist}

Plants’ ingenious defense against mutational damage

Mutation damages vital mitochondrial DNA and chloroplast DNA inside plant cells. New research from the CBU, with collaborators from Colorado, has shown how plants use randomness to deal with this damage. Published in New Phytologist (and featured on the cover as in the picture; you can watch a Youtube video summary and read the UiB news story), the team used mathematical models and new experiments to show how plants randomly “sort out” DNA as they develop. This ensures that some offspring of a damaged plant inherit intact DNA, preventing the full amount of damage being inherited from mother to offspring.

November 5, 2023

Postdoc Sean Alexander Bankier – new manuscript

Genome-wide association meta-analysis (GWAMA) by the Cortisol Network (CORNET) consortium identified genetic variants spanning the SERPINA6/SERPINA1 locus on chromosome 14 associated with morning plasma cortisol, cardiovascular disease (CVD), and SERPINA6 mRNA expression encoding corticosteroid-binding globulin (CBG) in the liver. These and other findings indicate that higher plasma cortisol levels are causally associated with CVD; however, the mechanisms by which variations in CBG lead to CVD are undetermined. Using genomic and transcriptomic data from …

September 8, 2023

_{Picture: Iain Johnston}

Socialising in the “flatland” of the plant cell

Chloroplasts catch light to power plants. Under stress, they form mysterious structures called “stromules”. Stromules are long, thin bits of membrane that stretch away from the chloroplast, and it’s not clear what they’re for. A new paper from a CBU-Halle collaboration (featured as a highlight) in Plant and Cell Physiology explores these structures. It shows that in many plant cells, the environment is very thin (less than a micron wide). Computational modelling shows that stromule formation is an efficient way for chloroplasts to interact with other parts of the cell in this remarkable “flatland”.

September 2, 2023

Probing the structure of individual RNA molecules

RNA molecules can form secondary and tertiary structures that can regulate their localization and function. These structures are rarely static and different copies of the same RNA can often adopt many different conformations. Despite this most methods are only capable of characterizing RNA at the consensus level, looking at the average over RNA molecules.

A new paper in Nucleic Acids Research from Teshome Bizuyaheu in the Valen group addresses this by developing a method to probe for structure …

October 28, 2022

Structure of POPC Lipid Bilayers in OPLS3e Force Field

It is crucial for molecular dynamics simulations of biomembranes that the force field parameters give a realistic model of the membrane behavior. In this study, we examined the OPLS3e force field for the carbon–hydrogen order parameters S_CH of POPC (1-palmitoyl-2-oleoylphosphatidylcholine) lipid bilayers at varying hydration conditions and ion concentrations. The results show that OPLS3e behaves similarly to the CHARMM36 force field and relatively accurately follows the experimentally measured S_CH for the lipid headgroup, the glycerol backbone, and the acyl tails. Thus, OPLS3e is a …

September 8, 2022