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Telling Lab

While the Telling Laboratory is particularly recognized for their work on transgenic mouse modeling of prion diseases, it is one of only a handful of research groups with the resources and expertise for studying prion diseases using whole animal, transgenic, cell biological, biochemical, and molecular genetic approaches. Over the years, we have been recognized for our studies of human prions, the molecular basis of the species barrier, prion strains and their zoonotic potential, and, more recently, chronic wasting disease (CWD) of cervids.

Our ability to liaise and collaborate with the prion community is also significant. In combination with skills and perspectives provided by our talented collaborators, the Telling Laboratory is in a unique position to investigate the molecular events underlying prion propagation, species barriers and strains, which remain the overarching goals of Dr. Telling’s research program.

research project

NIH Program Project Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases: Modeling the Mechanisms of Prion Transmission, Strain Selection, Mutation and Species Barrier in Transgenic Mice

In this PO1 we investigate the mechanism of infectious prion propagation. Emphasis is placed on studying the factors controlling interspecies transmission. The central hypothesis of this work is that prion species barriers and agent strain properties are governed by primary and tertiary structural interactions between PrPSc constituting the infectious agent and PrPC expressed in the infected host.

research project

NIH Program Project Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases (P01): ‘Science Core’

The Telling lab operates the Science Core for this multicenter, multi-investigator Program. It provides experimental models, expertise, standardized and consistent methodologies, and high quality reagents to allow investigators to study the molecular mechanisms of prion replication, the factors controlling the species barrier and the role of the environment on CWD transmission.

research project

NIH R01 grant: Characterizing the strain and host range properties of prions causing emergent forms of chronic wasting disease

In this R01 project, the Telling lab is characterizing the transmission and conformational properties of CWD prions that have emerged in recent years in Norway and South Korea. A major goal is to compare the host-range properties and zoonotic potential of newly emergent CWD prion strains.

research project

NIH R01 grant: Mechanisms of prion strain dynamics

In this R01 project, the Telling lab employs cell culture and transgenic models of prion diseases to assess the mechanism of prion strain variation and selection.

research project

NIH R01 grant: Addressing the mechanisms of prion strain evolution and its effect on interspecies transmission

Our broad, long-term objectives are to assess and manage the risk posed to humans from continually evolving prions, specifically those causing chronic wasting disease (CWD), an uncontrollable contagious epidemic of cervids of uncertain zoonotic potential. Understanding the properties of emergent CWD strains, their origins, how they adapt and evolve, and their zoonotic threats are important goals.

Publications

Adaptive selection of a prion strain conformer corresponding to established North American CWD during propagation of novel emergent Norwegian strains in mice expressing elk or deer prion protein.

Bian J, Kim S, Kane SJ, Crowell J, Sun JL, Christiansen J, Saijo E, Moreno JA, DiLisio J, Burnett E, Pritzkow S, Gorski D, Soto C, Kreeger TJ, Balachandran A, Mitchell G, Miller MW, Nonno R, Vikøren T, Våge J, Madslien K, Tran L, Vuong TT, Benestad SL, Telling GC.
PLoS Pathog. 2021 Jul 26;17(7):e1009748. doi: 10.1371/journal.ppat.1009748. eCollection 2021 Jul.

Incomplete glycosylation during prion infection unmasks a prion protein epitope that facilitates prion detection and strain discrimination.

Kang HE, Bian J, Kane SJ, Kim S, Selwyn V, Crowell J, Bartz JC, Telling GC.
J Biol Chem. 2020 Jul 24;295(30):10420-10433. doi: 10.1074/jbc.RA120.012796. Epub 2020 Jun 8.

Primary structural differences at residue 226 of deer and elk PrP dictate selection of distinct CWD prion strains in gene-targeted mice.

Bian J, Christiansen JR, Moreno JA, Kane SJ, Khaychuk V, Gallegos J, Kim S, Telling GC.
Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12478-12487. doi: 10.1073/pnas.1903947116. Epub 2019 May 30.PMID: 31147460

Prion replication without host adaptation during interspecies transmissions.

Bian J, Khaychuk V, Angers RC, Fernández-Borges N, Vidal E, Meyerett-Reid C, Kim S, Calvi CL, Bartz JC, Hoover EA, Agrimi U, Richt JA, Castilla J, Telling GC.
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1141-1146. doi: 10.1073/pnas.1611891114. Epub 2017 Jan 17.PMID: 28096357