Blog Posts
NIH funding for mitochondrial apoptosis research.
The National Institutes of Health (NIH) have awarded the Van der Wel group a new R01 grant to support our research into the molecular mechanisms of mitochondrial apoptosis. Mitochondrial apoptosis is a vital cellular process required for proper development and health. However, malfunctioning of this process, e.g. undesired up- or down-regulation, plays a key role in diseases ranging from cancer to neurodegeneration, including Huntington’s Disease. In this project we investigate pivotal processes that occur early on in the apoptotic pathway, and thus may present important targets for medical intervention. A key focal point is on the role of mitochondrial membranes, and in particular the impact of changes in their structure, fluidity, and integrity. Our studies will leverage state-of-the-art ssNMR experiments, functional assays, and an array of biochemical and biophysical techniques.
Related Publications
- Structural changes and pro-apoptotic peroxidase activity of cardiolipin-bound mitochondrial cytochrome c. Mandal, A., Hoop, C.L., DeLucia, M., Kodali, R., Kagan, V., Ahn, J., Van der Wel, P.C.A.* (2015) Biophys. J. 109(9): 1873–1884 (DOI)
- Lipid Dynamics and Protein-Lipid Interactions in Integral Membrane Proteins: Insights from Solid-State NMR. Van der Wel, P.C.A.* (2014) eMagRes. 3: 111–118 (DOI) (PDF download)
Publication: Molecular structure and misfolding mechanism of expanded polyglutamine proteins.
In a new report in the journal Proceedings of the National Academy of Sciences of the USA (PNAS) we provide important new insights into the misfolding and aggregation behavior of the mutant protein that causes Huntington’s Disease (HD). First authors Dr Cody Hoop and Dr Hsiang-Kai (Kyle) Lin used advanced solid-state NMR spectroscopy to study the structure of fibrils formed by huntingtin exon1 and related polyglutamine proteins. These state-of-the-art experiments allow us to elucidate a new beta-hairpin-based structure for the polyglutamine fibril core. In addition, our results provide important new insights into the stochastic self-assembly mechanism of expanded polyglutamine. This protein misfolding mechanism is likely active not only in HD, but also in other CAG repeat expansion disorders. The newfound molecular understanding of these disease-causing processes may facilitate the rational design of aggregation-modulating treatments or drugs.
For more information, read the article at PNAS.
ENC NMR conference coming to Pittsburgh
This coming spring the Experimental NMR Conference (ENC) is returning to Pittsburgh. The ENC poster, including a list of invited speakers, is available here. To submit your abstract, go to this page by Jan 8th 2016 (which is the abstract deadline). The registration deadline is March 18th 2016.
Dates: April 10-15, 2016
Location: Wyndham Grand Pittsburgh Downtown
Program: ENC website
New ssNMR spectrometer update
The new NIH-funded 750MHz solid-state NMR instrument has now been delivered to the Department of Structural Biology NMR facility. It is currently being installed and configured.
NEW: Photos of the installation process are available in this online gallery.
This state-of-the-art instrument adds exciting new capabilities for advanced MAS ssNMR to the facility, such as the inclusion of new ‘very-fast’ MAS probes. The spectrometer will facilitate and enhance our ongoing studies of protein misfolding and aggregation in Huntington’s Disease, and studies of the protein-lipid interactions underlying cell death and neurodegeneration.
Biophysical Society meeting news!
Congratulations to Jennifer and Abhishek, for being selected for a talk and awarded travel grants for the coming Biophysical Society Meeting in San Diego! We look forward to seeing you there, and tell you more about our studies of protein deposition diseases and protein-lipid interactions.
Update: see also the press release by the Biophysical Society.
Publication: Solid-state NMR studies of the pro-apoptotic peroxidase-form of cytochrome c.
Congratulations to Abhishek and his co-authors!
The Biophysical Journal has accepted our paper on the structural and functional study of cardiolipin-bound cytochrome c, looking at its peroxidase activated membrane-bound state. Lipid oxidation by cytochrome c plays a critical role in mitochondrial apoptosis, and we examined the molecular underpinnings of this process using solid-state NMR spectroscopy and other tools.
For more information see the paper:
Mandal, A., Hoop, C.L., DeLucia, M., Kodali, R., Kagan, V., Ahn, J., Van der Wel, P.C.A.* (2015) Structural changes and pro-apoptotic peroxidase activity of cardiolipin-bound mitochondrial cytochrome c. Biophys. J. J. 109(9): 1873–1884 (Full text)
Great Lakes NMR Symposium
On Friday Sept. 11th, Case Western Reserve University is organizing the Great Lakes Regional NMR Symposium. Congratulations to Abhishek Mandal for being selected to present a seminar on his work on membrane protein structural and functional studies! We hope to see you there!
Congrats to Jennifer!
Congratulations to Jennifer, who successfully completed her candidacy exam for the MBSB PhD program! Well done!
Summer Science Nation visitors!
Today (July 15, 2015) we had a great visit to our department from participants in Carlow University’s Summer Science Nation workshop aimed at high school girls interested in science. Group members, students and other scientists from the Department of Structural Biology and the Molecular Biophysics and Structural Biology graduate program participated in facility tours and seminars, telling the visitors about some of the exciting fundamental biomedical research ongoing in the department and in Pittsburgh.
New spectrometer update (revised July ’15).
Our new wide-bore 750MHz solid-state NMR spectrometer (funded by the NIH High-End Instrumentation Award program) is scheduled to be installed during the summer (July 2015) in the fall of 2015. This will bring exciting new solid-state NMR capabilities, including lower temperature operation and ultra-fast MAS, among other things. Stay tuned for further updates!