Michael Nash


Last Name

Nash

First Name

Michael

ORCID

0000-0003-3842-1567

Organisational unit

09586 - Nash, Michael / Nash, Michael

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2016 - 2019192020 - 202530
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Publications 1 - 10 of 49
  • Steered molecular dynamics simulations reveal the role of Ca2+ in regulating mechanostability of cellulose-binding proteins
    Item type: Journal Article
    Gunnoo, Melissabye; Cazade, Pierre-Andre; Orlowski, Adam; et al. (2018)
    Physical Chemistry Chemical Physics
  • Zig Zag AFM Protocol Reveals New Intermediate Folding States of Bacteriorhodopsin
    Item type: Review Article
    Nash, Michael (2020)
    Biophysical Journal
  • Enzyme‐mediated hydrogel encapsulation of single cells for high‐throughput screening and directed evolution of oxidoreductases
    Item type: Journal Article
    Vanella, Rosario; Ta, Duy Tien; Nash, Michael (2019)
    Biotechnology and Bioengineering
  • Protein Engineering and High-Throughput Screening by Yeast Surface Display: Survey of Current Methods
    Item type: Review Article
    Lopez-Morales, Joanan; Vanella, Rosario; Appelt, Elizabeth A.; et al. (2023)
    Small Science
    Yeast surface display (YSD) is a powerful tool in biotechnology that links genotype to phenotype. In this review, the latest advancements in protein engineering and high-throughput screening based on YSD are covered. The focus is on innovative methods for overcoming challenges in YSD in the context of biotherapeutic drug discovery and diagnostics. Topics ranging from titrating avidity in YSD using transcriptional control to the development of serological diagnostic assays relying on serum biopanning and mitigation of unspecific binding are covered. Screening techniques against nontraditional cellular antigens, such as cell lysates, membrane proteins, and extracellular matrices are summarized and techniques are further delved into for expansion of the chemical repertoire, considering protein-small molecule hybrids and noncanonical amino acid incorporation. Additionally, in vivo gene diversification and continuous evolution in yeast is discussed. Collectively, these techniques enhance the diversity and functionality of engineered proteins isolated via YSD, broadening the scope of applications that can be addressed. The review concludes with future perspectives and potential impact of these advancements on protein engineering. The goal is to provide a focused summary of recent progress in the field.
  • Influence of Fluorination on Single-Molecule Unfolding and Rupture Pathways of a Mechanostable Protein Adhesion Complex
    Item type: Journal Article
    Yang, Byeongseon; Liu, Haipei; Liu, Zhaowei; et al. (2020)
    Nano Letters
    We investigated the influence of fluorination on unfolding and unbinding reaction pathways of a mechanostable protein complex comprising the tandem dyad XModule-Dockerin bound to Cohesin. Using single-molecule atomic force spectroscopy, we mapped the energy landscapes governing the unfolding and unbinding reactions. We then used sense codon suppression to substitute trifluoroleucine in place of canonical leucine globally in XMod-Doc. Although TFL substitution thermally destabilized XMod-Doc, it had little effect on XMod-Doc:Coh binding affinity at equilibrium. When we mechanically dissociated global TFL-substituted XMod-Doc from Coh, we observed the emergence of a new unbinding pathway with a lower energy barrier. Counterintuitively, when fluorination was restricted to Doc, we observed mechano-stabilization of the non-fluorinated neighboring XMod domain. This suggests that intramolecular deformation is modulated by fluorination and highlights the differences between equilibrium thermostability and non-equilibrium mechanostability. Future work is poised to investigate fluorination as a means to modulate mechanical properties of synthetic proteins and hydrogels.
  • Phase Separation of Intrinsically Disordered Protein Polymers Mechanically Stiffens Fibrin Clots
    Item type: Journal Article
    Urosev, Ivan; Lopez Morales, Joanan; Nash, Michael (2020)
    Advanced Functional Materials
    Fibrin (Fb) networks self-assemble through the coagulation cascade and serve as the structural foundation of blood clots. Following severe trauma or drug therapy, reduced integrity of Fb networks can lead to formation of clots with inadequate mechanical properties. A key feature of therapeutic interventions for hemostasis is therefore the ability to restore mechanical strength to clots formed under coagulopathic conditions. Here, an intrinsically disordered protein based on an elastin-like polypeptide (ELP) sequence is described, which specifically binds Fb and modulates its mechanical properties. Hemostatic ELPs (hELPs) are designed containing N- and C-terminal peptide tags that are selectivity recognized by human transglutaminase factor XIIIa and covalently linked into fibrin networks via the natural coagulation cascade. Phase separation of hELPs above their lower critical solution temperature leads to stiffening and rescue of clot biophysical properties under simulated conditions of dilutive coagulopathy. In addition to phase-dependent stiffening, the resulting hELP-Fb networks exhibit resistance to plasmin degradation, reduced pore sizes, and accelerated gelation rate following initiation of clotting. These results demonstrate the ability of protein-based phase separation to modulate the physical and biochemical properties of blood clots and suggest protein phase separation as a new mechanism for achieving hemostasis in clinical settings.
  • Elastin-like Polypeptides: Protein-based Polymers for Biopharmaceutical Development
    Item type: Other Journal Item
    Nash, Michael (2022)
    Chimia
  • Scalable Online Learning in Physical Chemistry
    Item type: Other Journal Item
    Nash, Michael (2021)
    Chimia
    The SARS-CoV-2/COVID-19 pandemic has disrupted higher education across the globe. As of early November 2020, Europe now finds itself in the middle of a second wave that is even more destructive than the first. The Swiss Federal Council declared on 28 October, 2020 that face-to-face teaching at Swiss Universities was to cease within days. With large introductory lectures in natural science faculties forced entirely online, educators in Switzerland are facing new challenges and dealing with the limitations of remote instruction. Through a series of anecdotes and observations, this article identifies challenges associated with scalable online learning, and explores methods to mitigate them. Additionally, several advantages to scalable online instruction are identified. By focusing on areas where online instruction has significant advantages, I argue that we can deliver high quality instruction in the chemical sciences remotely.
  • Bioorthogonal Elastin-like Polypeptide Scaffolds for Immunoassay Enhancement
    Item type: Journal Article
    Ta, Duy Tien; Vanella, Rosario; Nash, Michael (2018)
    ACS Applied Materials & Interfaces
  • Engineered Stochastic Adhesion Between Microbes as a Protection Mechanism Against Environmental Stress
    Item type: Journal Article
    Lewis, Daniel D.; Vanella, Rosario; Vo, Christopher; et al. (2018)
    Cellular and Molecular Bioengineering
Publications 1 - 10 of 49