Author: dean_lung

Our recent article published in Disease Models & Mechanisms, ‘A method for TAT-Cre recombinase-mediated floxed allele modification in ex vivo tissue slices’, was one of the most-read articles published in the November issue. Click here to read the article.

This recognition not only validates our efforts but also underscores the significance of the innovative TReATS method we’ve developed. We’re delighted to see that the paper has been well-received by the readers, and we hope that the TReATS method will continue to benefit the scientific community.

Additionally, our contribution has also planted a tree in The Forest of Biologists.

On 1^st November, members of the lab attended a newly established annual meeting on ‘Signalling Molecules in Disease’ held at Kingston University. The aim of the symposium was to create a community of researchers who study cell signalling across all disease fields. The meeting was very informative with a variety of talks on everything from cancer to Schistosomiasis.

There was also a poster session which provided junior researchers with an excellent opportunity to present their work to a broad audience. Esther presented a poster on her PhD work ‘Using in vitro and ex vivo models of lung injury as a platform to identify and study mechanisms driving lung repair’. The plan is for this meeting to become an annual event.

Exciting news from our lab! We have just published a paper in Disease Models & Mechanisms detailing the ground-breaking TReATS (TAT-Cre Recombinase-mediated Floxed Allele Modification in Tissue Slices) method—a revolutionary approach to gene manipulation in precision-cut lung slices (PCLS).

PCLS have long been invaluable tools for researchers in respiratory research due to their versatility and physiological relevance. However, methods to manipulate genes in tissue slices remain limited.

Our TReATS method successfully induced highly effective and controlled gene deletion or activation in ex vivo 3D adult PCLS using cell-permeant TAT-Cre recombinase.

The significance of TReATS lies not only in its ability to induce highly effective and temporally controlled gene deletion or activation but also in its capacity to bypass the conventional hurdles of Cre-Lox breeding. This innovation allows researchers to circumvent issues related to embryonic lethality, and enables recombination across multiple cell types simultaneously in adult tissue slices.

The implications of this methodology are far-reaching. TReATS opens new avenues for accelerated and highly effective gene manipulation, facilitating the study of the functional consequences of genetic modifications in a controlled and reproducible ex vivo environment.

Click here to read the full article

As the first author of this article, Sek-Shir has been chosen for the first-person interview.

To explore her insights and responses to the interview questions, kindly follow this link: First-person interview

The Lung Development & Repair group attended the third annual NHLI Research Away Day, held on 25 September 2023 at the Queen Elizabeth II Conference Centre. It was a great opportunity to learn about exciting research from across the institute on hot topics in the field!

Rebecca presented a poster on “Investigating injury- and ageing-related alterations in lung tissue-derived extracellular vesicles and their effects on lung tissue”, exploring for the first time the therapeutic potentials of extracellular vesicles derived from precision cut lung slices, using the acid injury repair (AIR) model recently established by our lab.

‘Engineering Translational Models of Lung Homeostasis and Disease’

We are delighted to announce the release of “Engineering Translational Models of Lung Homeostasis and Disease”. Dr. Charlotte Dean and Dr. Sek-Shir Cheong contributed a chapter to this book entitled ‘Simple Models of Lung Development’. We wanted to share some insights about this exciting publication.

This book pushes the boundaries of interdisciplinary collaboration in the realm of lung research. By integrating established knowledge in lung biology and physiology with innovative engineering strategies, this publication aims to foster advancements and facilitate a deeper understanding of lung disease for researchers, clinicians, and medical practitioners.

A distinguishing feature of the book is its systematic exploration of specific lung regions, presenting an integrated perspective that seamlessly combines biological and clinical viewpoints with complementary engineering approaches. By bridging the gap between engineering and lung biology, the text provides an ideal platform to delve into emerging models that enhance our understanding of lung disease and repair processes.

Notably, “Engineering Translational Models of Lung Homeostasis and Disease” not only highlights the current translational challenges faced in the field but also unveils exciting engineering opportunities to overcome these obstacles. The book serves as a catalyst for interdisciplinary collaboration and offers valuable insights for researchers and clinicians across disciplines such as engineering, materials science, cell biology, pulmonary medicine, and clinical science. To learn more or to secure your copy of the book, please visit the official publication page:

https://link.springer.com/book/10.1007/978-3-031-26625-6

Sally and Charlotte attended the Tissue Engineering and Regenerative Medicine International Society European Chapter (TERMIS-EU) Meeting 2023 at Manchester, UK on 28-31 March (https://eu2023.termis.org/).

Sally presented ‘The pro-repair effects of tissue-derived extracellular vesicles are modified with ageing’ at the Respiratory tissue and engineering and regeneration session and Charlotte presented a poster on the AIR model, ‘AIR – A novel ex-vivo model for studies of tissue repair’.

We are excited to welcome back Rebecca Chen to begin her PhD. Rebecca completed her masters project in the lab, finishing in September 2021. Working with Sally Kim, Rebecca looked at the effects of lung-derived extracellular vesicles on repair in young versus aged lungs. Rebecca’s PhD project will utilise the skills and knowledge she gained during her masters to investigate ‘extracellular vesicle-derived therapeutic approaches for lung repair’.

The project combines our long-standing interest in determining how Wnt signalling contributes to lung development and repair with bioengineering approaches to target protein delivery to the lungs.

We will determine whether administering Wnt5a (a potential pro-repair protein) to the lungs can strengthen the capacity that the lungs already have to repair themselves. This protein has been shown to stimulate lung stem cells after injury occurs and it is these stem cells that are needed to drive the lung repair process. However we don’t yet understand exactly how the Wnt5a protein carries out this key role and this is what we will determine. We will use time-lapse imaging to video the response of lung cells to Wnt5a treatment and track exactly how this protein stimulates repair. As part of this proposal we will also encase Wnt5a protein in tiny particles of gel and formulate a Wnt5a-gel treatment that can be administered to the lungs to stimulate repair. Encasing Wnt5a in a degradable gel will enable sustained and targeted administration of this treatment.

Dr Sally Kim has been integral to the development of this project which she will co-lead through her role as a researcher co-investigator.

After being postponed for 2 years, NHLI Research Away Day was back again!

The Away Day was held on a beautiful day on Friday 17 June 2022 at the Queen Elizabeth II Conference Centre. It was a great opportunity for all staff and students to meet colleagues and to learn the breadth of research across NHLI!

Dr Sek-Shir Cheong gave a talk on ‘Temporal Control of DNA recombination and mRNA delivery in ex vivo Precision-Cut Lung Slices’, describing novel methods that our lab recently established to manipulate genes/targets in adult tissue-based models.