Novel Nanobodies: The Use of Heavy-Chain Only Antibody Fragments to Study Protein Function – UROP Spring Symposium 2022

Novel Nanobodies: The Use of Heavy-Chain Only Antibody Fragments to Study Protein Function

photo of presenter

Yasmeen Berry

Pronouns: she/her/hers

Research Mentor(s): Matthias Truttmann
Co-Presenter:
Research Mentor School/College/Department: molecular and integrative physiology / Medicine
Presentation Date: April 20
Presentation Type: Oral10RS
Session: Session 6 – 4:40pm – 5:30 pm
Room: Vandenberg
Authors: Yasmeen Berry, Nicholas Urban, Matthias Truttmann
Presenter: 1

Abstract

Nanobodies are heavy-chain only antibody fragments which can replace and often outcompete traditional antibodies in a variety of research applications. They combine the binding specificity of antibodies with nanoscale delivery. In addition to this, nanobodies provide a cost-effective, quick, and technically simple means of production. Due to the lack of high-quality traditional antibodies to study the protein homeostasis (proteostasis) network, which has been shown to decline with increased age and in neurodegenerative diseases, we recently produced and validated nanobodies against key components of the proteostasis network (FICD, HSP-1, and HSC70) for use in in vitro applications (e.g Western blotting, ELISA). We show that one of these nanobodies inhibits protein function in vitro. Thus, we generated a novel C. elegans model to study the effect of inducible expression of this nanobody in vivo. Our preliminary data indicate expression of this nanobody targeting HSP-1 (the HSC70 ortholog, an essential chaperone protein) decreases worm viability. This is, to the best of our knowledge, the first indication of a nanobody being able to modulate organismal physiology in vivo in C. elegans. Ongoing efforts include investigating the effect of nanobody expression in neurodegenerative disease models and panning for new nanobodies against FICD, and other proteins of interest in the proteostasis network, from our newly generated nanobody phagemid library. Overall, our results show that nanobodies have the potential to be utilized in a broad range of potential research applications. This includes studying protein function in vitro and in vivo within the context of disease.

Presentation link

Biomedical Sciences, Natural/Life Sciences

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