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3 results on '"Tasja Wainani Ebersole"'

1. In vivo neutralization of coral snake venoms with an oligoclonal nanobody mixture in a murine challenge model

Author

Melisa Benard-Valle, Yessica Wouters, Anne Ljungars, Giang Thi Tuyet Nguyen, Shirin Ahmadi, Tasja Wainani Ebersole, Camilla Holst Dahl, Alid Guadarrama-Martínez, Frederikke Jeppesen, Helena Eriksen, Gibran Rodríguez-Barrera, Kim Boddum, Timothy Patrick Jenkins, Sara Petersen Bjørn, Sanne Schoffelen, Bjørn Gunnar Voldborg, Alejandro Alagón, and Andreas Hougaard Laustsen

Subjects
Science
Abstract

Abstract Oligoclonal mixtures of broadly-neutralizing antibodies can neutralize complex compositions of similar and dissimilar antigens, making them versatile tools for the treatment of e.g., infectious diseases and animal envenomations. However, these biotherapeutics are complicated to develop due to their complex nature. In this work, we describe the application of various strategies for the discovery of cross-neutralizing nanobodies against key toxins in coral snake venoms using phage display technology. We prepare two oligoclonal mixtures of nanobodies and demonstrate their ability to neutralize the lethality induced by two North American coral snake venoms in mice, while individual nanobodies fail to do so. We thus show that an oligoclonal mixture of nanobodies can neutralize the lethality of venoms where the clinical syndrome is caused by more than one toxin family in a murine challenge model. The approaches described may find utility for the development of advanced biotherapeutics against snakebite envenomation and other pathologies where multi-epitope targeting is beneficial.

Published
2024
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2. Molecular Basis of the Mechanisms Controlling MASTL

Author

Giuseppe Cazzamali, Gulnahar B. Mortuza, Anna-Kathrine Pedersen, Irina Pozdnyakova, Tam T.T.N. Nguyen, Guillermo Montoya, Kasper D. Rand, Tasja Wainani Ebersole, Michael Williamson, Dario Hermida, Jesper V. Olsen, Marcos Malumbres, and María Maroto

Subjects
0303 health sciences, Cyclin-dependent kinase 1, Kinase, Chemistry, Research, 030302 biochemistry & molecular biology, Autophosphorylation, Phosphatase, Protein Serine-Threonine Kinases, Biochemistry, Catalysis, Analytical Chemistry, Cell biology, Serine, Dephosphorylation, 03 medical and health sciences, HEK293 Cells, Protein kinase domain, Cell Line, Tumor, Humans, Phosphorylation, Microtubule-Associated Proteins, Molecular Biology, Gene, 030304 developmental biology
Abstract

The human MASTL (Microtubule-associated serine/threonine kinase-like) gene encodes an essential protein in the cell cycle. MASTL is a key factor preventing early dephosphorylation of M-phase targets of Cdk1/CycB. Little is known about the mechanism of MASTL activation and regulation. MASTL contains a non-conserved insertion of 550 residues within its activation loop, splitting the kinase domain, and making it unique. Here, we show that this non-conserved middle region (NCMR) of the protein is crucial for target specificity and activity. We performed a phosphoproteomic assay with different MASTL constructs identifying key phosphorylation sites for its activation and determining whether they arise from autophosphorylation or exogenous kinases, thus generating an activation model. Hydrogen/deuterium exchange data complements this analysis revealing that the C-lobe in full-length MASTL forms a stable structure, whereas the N-lobe is dynamic and the NCMR and C-tail contain few localized regions with higher-order structure. Our results indicate that truncated versions of MASTL conserving a cryptic C-Lobe in the NCMR, display catalytic activity and different targets, thus establishing a possible link with truncated mutations observed in cancer-related databases.

Published
2020
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3. Production of functional human insulin-like growth factor binding proteins (IGFBPs) using recombinant expression in HEK293 cells

Author

Michael Williamson, Giuseppe Cazzamali, Werner Streicher, Mats Wikström, Tasja Wainani Ebersole, and Anne Sofie Molsted Wanscher

Subjects
Drug discovery, Recombinant expression, Growth factor, medicine.medical_treatment, HEK 293 cells, Gene Expression, Biology, Molecular biology, DNA-binding protein, Recombinant Proteins, law.invention, Insulin-Like Growth Factor Binding Proteins, HEK293 Cells, Biochemistry, law, Insulin-Like Growth Factor II, Protein purification, medicine, Recombinant DNA, Humans, Signal transduction, Insulin-Like Growth Factor I, Biotechnology
Abstract

Insulin-like growth factor binding proteins (IGFBPs) display many functions in humans including regulation of the insulin-like growth factor (IGF) signaling pathway. The various roles of human IGFBPs make them attractive protein candidates in drug discovery. Structural and functional knowledge on human proteins with therapeutic relevance is needed to design and process the next generation of protein therapeutics. In order to conduct structural and functional investigations large quantities of recombinant proteins are needed. However, finding a suitable recombinant production system for proteins such as full-length human IGFBPs, still remains a challenge. Here we present a mammalian HEK293 expression method suitable for over-expression of secretory full-length human IGFBP-1 to -7. Protein purification of full-length human IGFBP-1, -2, -3 and -5 was conducted using a two-step chromatography procedure and the final protein yields were between 1 and 12 mg protein per liter culture media. The recombinant IGFBPs contained PTMs and exhibited high-affinity interactions with their natural ligands IGF-1 and IGF-2.

Published
2014

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