CDB labs have a raft of papers published early 2024

7 March 2024

Labs headed by Patricia Salinas, Claudio Stern, Jason Rihel, Sandip Patel, Richard Poole and Susan Evans have had paper(s) published so far this year (2024). We report here on the Salinas, Stern, Rihel and Patel news, with Poole's and Evans' each appearing in separate articles.

Image related to downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer’s disease (AD), which restores synapse integrity and memory in a disease mouse model

Patricia Salinas’ lab and co-researchers recently published a paper in eLife entitled “Downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer’s disease (AD), restores synapse integrity and memory in a disease mouse model”. Synapse dysfunction is one of the earliest hallmarks of AD, but the mechanisms involved are not fully understood, but Wnt signalling has been implicated. The authors demonstrate a novel role for DKK3, which negatively regulates Wnt signalling, in regulating excitatory and inhibitory synaptic integrity. The image was obtained from Martin-Flores, Podpolny et al., eLife (2024).

Claudio Stern’s lab is delighted that Hyung Chul Lee et al’s paper on the Regulation of long-range BMP gradients and embryonic polarity by propagation of local calcium-firing activity has – after a long wait – been published in Nature Communications (https://www.nature.com/articles/s41467-024-45772-4). Hyung Chl Lee is now based at the Chonnam National University in Korea. Many amniote vertebrate species, including humans, can form identical twins from a single embryo, but this rarely occurs. It has been suggested that the primitive-streak-forming embryonic region emits signals that inhibit streak formation elsewhere, but how the signals involved, how they are transmitted and how they act has not before been elucidated. This research provides evidence for similar mechanisms in two different human embryo models and in Drosophila, suggesting an ancient evolutionary origin.

Photo of Güliz Gürel Özcan, lead author from RIhel lab of paper on amyloid precursor protein in zebrafish

The Rihel lab has had a new paper accepted for publication in iScience on: Genetic and chemical disruption of amyloid precursor protein processing impairs zebrafish sleep maintenance, authored by Güliz Gürel Özcan, Sumi Lim, Thomas Canning, Lavitasha Tirathdas, Joshua Donnelly, Tanushree Kundu, Jason Rihel. The pre-proof is available here: Genetic and chemical disruption of Amyloid Precursor Protein processing impairs zebrafish sleep maintenance” - ScienceDirect. This work investigated whether modulation of the amyloid precursor protein (APP), which is cleaved to make the toxic amyloid-beta species that build up in Alzheimer’s disease, has effects on sleep in zebrafish. The authors found that losing one form of APP leads to more fragmented sleep at night, and also that another amyloid-beta-related protein called P3 also affects sleep in zebrafish.

Additionally, this work is the first to show definitively that zebrafish naturally produce amyloid-beta, something that previous work had assumed but not formally demonstrated. The photo is of first-named author, Güliz Özcan. The work was funded by the Wellcome Trust and a Fellowship to Güliz from the Alzheimer’s Research UK charity.

Image of Cell Reports paper (article) on 30 December 2023

Sandip Patel’s lab sends congratulations to Yu (‘Cara’) Yuan, a post-doc in the lab, on her recent work published in Cell Reports. The work was a team effort with other members of the lab, namely: Ryo Saito (now back in Japan), Qianru (‘Maggie’) Mu and Steve Bolsover (now retired), and international partners principally David Yule’s lab at the University of Rochester, USA. Their data provide a conceptual framework to understand how Ca²⁺ release from physically separated stores, such as lysosomes and the endoplasmic reticulum (ER) is coordinated. Full paper at: https://www.cell.com/cell-reports/fulltext/S2211-1247(23)01639-X