Congratulations to Abhishek for his successful PhD defense!
Congratulations to Abhishek, for defending his PhD thesis entitled “Investigations of the structural changes in proapoptotic peroxidase-active cardiolipin-bound cytochrome c and liquid-gel phase transitions in liposomes using solid state NMR spectroscopy.” Abhishek has been a PhD student in the Pitt/CMU PhD program in Molecular Biophysics & Structural Biology (MBSB).
Congratulations, Dr. Mandal!
Welcoming two new postdoctoral researchers!
We are excited to welcome two new postdoctoral researchers to the lab, who joined us this November 2016. Dr. Irina Matlahov is joining us from Bar-Ilan University in Israel, where she did her PhD research in solid-state NMR spectroscopy. Dr. Mingyue Li is joining us from the University of Delaware, where she also worked on biomolecular solid-state NMR. They will be working on our NIH-funded research projects on the protein misfolding and aggregation processes associated with Huntington’s Disease and the pivotal membrane-protein interactions implicated in mitochondrial apoptosis.
For more information, see the People page of the site.
Publication: MAS NMR studies of lipid phase behavior at low temperatures. (Biophys J)
Congratulations to Abhishek Mandal for his new paper in the Biophysical Journal. You can gain free access to the paper through the following URL (until Dec 2016). In this paper Abhishek describes his use of magic-angle-spinning NMR and differential scanning calorimetry (DSC) to look at the freezing and melting of water and lipids in hydrated membrane samples. Detecting the lipid and water proton nuclei by NMR, we observe a change in the freezing temperature of the water and the gel-liquid transition of the phospholipids (including also cardiolipin (TOCL)-containing samples). The MAS NMR sample conditions lower the freezing point of the water, but also lead to a lowering of the lipids Tm temperature. For more information read the paper here.
MAS 1H NMR Probes Freezing Point Depression of Water and Liquid-Gel Phase Transitions in Liposomes
Abhishek Mandal, Patrick C.A. van der Wel
Biophysical Journal, Volume 111, Issue 9, 1 November 2016, Pages 1965–1973
Publication: structural and functional study of peptide-based nano-structures (JACS).
Congrats to our collaborators in the Rosi group (Pitt chemistry), the Zhang group (Struct. Biol. Dept.) and co-authors, on the acceptance of our collaborative paper in JACS, describing the structural and functional analysis of peptide-based nano-assemblies. The paper is available online as an in-press “ASAP” article on the JACS website. Jennifer and Abhishek used solid-state NMR to probe the core structure of the assembled peptides, finding a type of “intrinsic” polymorphism indicative of amyloid-like “steric zipper” motifs in these designer nanomaterials.
NIH T32 fellowship awarded to graduate student Jennifer Boatz!
Congratulations to lab member Jennifer Boatz! Jennifer was awarded one of the NIH/NIGMS-funded T32 fellowships (T32GM088119) of the Molecular Biophysics & Structural Biology graduate program. Starting this September, the T32 fellowship will help support her research into the molecular mechanisms of disease-associated protein aggregation, using solid-state NMR and other structural and biophysical techniques.
Congratulations to Jennifer!
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.
- 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.
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.