Author: Patrick
New Publication on Lipid Oxidation
Now online in the journal Free Radical Biology and Medicine: a new review and perspective article by our collaborator Valerian Kagan (Univ. Pittsburgh). The paper (titled “Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death”) examines the role of controlled lipid oxidation as a source of vital cellular signals. In particular it reviews recent work showing how cardiolipins and phosphatidylethanolamine lipids are oxidised by enzymes, as triggers of apoptosis and ferroptosis. Interestingly, the enzymatically generated oxidised species are distinct from those generated by spontaneous peroxidation, which may be important for the regulatory role of these species.
For more details, read the whole article here:
Kagan et al. (2020) “Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death” Free Radical Biology and Medicine, Vol. 147, pp. 231-241
MAS ssNMR @ RuG arrived and operational (mostly)
Instrumentation update:
Our new 600 MHz NMR spectrometer from Bruker Biospin has arrived and been installed in building 5113 on the Zernike campus of the University of Groningen. The system features a new high-performance NEO-style console, with the necessary solid-state NMR (ssNMR) accessories. Although the ordered magic-angle-spinning (MAS) ssNMR probes are not yet available, a preliminary MAS ssNMR probe has been successfully installed.
For now, a few components are still missing, and the field remains a bit unstable. However, preliminary experiments have started! Further updates to follow.
For more information on our capabilities and for information about usage please contact the PI (p.c.a.van.der.wel@rug.nl) and/or our NMR technician (a.lasorsa@rug.nl).
Publication: New review article on the structural biology of Huntington’s disease.
Now online at the journal Experimental Biology and Medicine: our new review article summarizing recent contributions from solid-state NMR and electron microscopy to further our understanding of the (mis)behavior of the mutant proteins behind Huntington’s disease.
Citation:
I. Matlahov & P.C.A. van der Wel (2019) Conformational studies of pathogenic expanded polyglutamine protein deposits from Huntington’s disease. Exp. Biol. Med. in press; DOI: 10.1177/1535370219856620
Publication: cytochrome c-cardiolipin complexes as pro-apoptotic lipid peroxidase.
Our first paper of 2019 has just appeared online in the journal Structure. It describes the very nice solid-state NMR studies performed by Dr. Mingyue Li, on a protein-lipid complex involved in the early stages of mitochondrial apoptosis. Together with our collaborators in the groups of Valerian Kagan and Jinwoo Ahn (University of Pittsburgh), she looked at the structure and function of the peroxidase active cytochrome c in its membrane-bound state. For more details on the findings, including how the lipid substrate cardiolipin forms membrane nano domains and acts as a dynamic regulator, please see the paper at the journal. This work was made possible by NIH funding (NIGMS R01 GM113908).
Reference:
Surface-Binding to Cardiolipin Nanodomains Triggers Cytochrome c Pro-apoptotic Peroxidase Activity via Localized Dynamics. Li, M., Mandal, A., Tyurin, V.A., Delucia, M., Ahn, J., Kagan, V.E., & Van der Wel, P.C.A. (2019) Structure, in press [URL]
Additional information/press info:
New PhD position available – polyglutamine structural biology.
Update: this position has been filled!
26/02/2019: A new fully-funded PhD position in the lab is available in our project studying the structure of polyglutamine amyloid proteins involved in Huntington’s disease. This research position will focus to a large extent on continuing and expanding the structural ssNMR methods that we previously reported in:
• Hoop et al. Huntingtin exon 1 fibrils feature an interdigitated β-hairpin-based polyglutamine core. Proc. Natl. Acad. Sci. USA. 2016 Feb 9;113(6):1546–51.
This will involve the development, testing and application of advanced ssNMR structural measurements. Aside from the ssNMR development work, structural measurements will be integrated with mechanistic and biological assays, similar to prior our paper:
• Lin et al. Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core. Nat Commun. 2017 May 24;8:15462.
The applicant is also expected to be comfortable with the English language and enthusiastic about working in a collaborative team environment. The ideal candidate would have a relevant MSc degree in physics or chemistry, experience with NMR spectroscopy, and a genuine interest in (bio)physics and protein structural biology. Interested individuals with a different, but relevant, background are encouraged to inquire. Inquiries, questions, and applications should be sent by email to p.c.a.van.der.wel@rug.nl. Applications should include a CV, a cover letter describing your motivation for being interested in the project and contact information for two or three reference writers.
Also posted here.
12/03/2019 – update – the funding organisation (Campagneteam Huntington) has posted a news item about their support of this research project.
Update on New Feringa Building
Exciting news about the upcoming construction of a brand new building for the lab and the Institute. Construction of the new Feringa Building at the RUG will commence later this year, to be completed in 2021. For more see link:
https://www.rug.nl/groundbreakingwork/190222_feringa_building_construction_agreement
Looking for NMR research technician (MSc/PhD)
More information to follow later, but we just posted the official advertisement for a new research technician with a NMR/SSNMR background. For details see here:
https://www.rug.nl/about-us/work-with-us/job-opportunities/overview?details=00347-02S0006SAP
The deadline is Feb 14th, 2019. Applications should be done via the above URL.
Publication: new collaborative paper on DNP/ssNMR-enabled studies at natural abundance (JACS).
Congrats to Talia, Jennifer and Irina, as well as our international network of collaborators on the acceptance of an exciting new paper in JACS. It describes the power of dynamic nuclear polarization (DNP) to enable multidimensional solid-state NMR studies of polyglutamine-expanded huntingtin exon 1 fibrils. Importantly in these experiments we did not apply stable-isotope labeling to these protein deposits that are implicated in Huntington’s disease. This approach enables great structural data and can hopefully prove applicable to many more (types of) samples.
More info to follow, but for now: Read the accepted paper here at the journal.
Title: Structural fingerprinting of protein aggregates by DNP-enhanced solid-state NMR at natural isotopic abundance
Authors: Adam N. Smith, Katharina Märker, Talia Piretra, Jennifer C. Boatz, Irina Matlahov, Ravindra B. Kodali, Sabine Hediger, Patrick C.A. van der Wel, and Gaël De Paëpe
DOI: 10.1021/jacs.8b09002
New PhD position(s) available in Groningen.
Please visit the “Join?” page for information about new PhD position(s) opening up in the lab at the University of Groningen. Or:
University of Groningen, the Netherlands
Starting in Aug. 2018, the solid-state NMR group of Prof. Van der Wel has moved to the Zernike Institute for Advanced Materials at the University of Groningen. This brings Prof. Van der Wel back to the Netherlands after many years in the USA.
Please also see the announcement here: https://www.rug.nl/research/zernike/news/newsitems/201808_vdwel
We look forward to continuing our interdisciplinary collaborative research with new and old collaborators across the globe. For a while the group will be in transition. Please stay posted for further news, updates and exciting new papers.
Selected Links:
- ZIAM announcement
- ZIAM homepage
- University of Groningen homepage
- Groningen, The Netherlands on wikipedia