Blog Posts

Our new publication together with our collaborators in the Wetzel and Horne groups is now available online at the Journal of Molecular Biology:

• Backbone engineering within a latent β-hairpin structure to design inhibitors of polyglutamine amyloid formation. Kar, K., Baker, M.A., Lengyel, G.A., Hoop, C.L., Kodali, R., Byeon, I-J., Horne, W.S., Van der Wel, P.C.A., and Wetzel, R., (2016) J. Mol. Biol. in press (DOI)

In this work, Karunakar Kar and co-workers (including Cody Hoop from our lab) combined various techniques to design and test designer-inhibitors against polyQ aggregation. The work highlights the value of structural and mechanistic understanding of the polyglutamine misfolding and aggregation process in such endeavors. (Some of these structural insights were derived from current and prior solid-state NMR studies.)

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!

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.

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 T_m temperature. For more information read the paper here.

Reference:
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

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.

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!