News

MSc project on ‘Investigating lung architecture and development in Down syndrome mouse mutants’

“I was made to feel a part of the team as I attended weekly laboratory meetings with the group, which enabled me to keep up with and gain an understanding of the current research” – Onyinyechi

“As part of my master’s degree in Cardiovascular and Respiratory Healthcare at Imperial College London, I spent four months with the Dean group. Here I undertook a research project that investigated lung development in mouse models of Down syndrome. I was supervised by Charlotte Dean and Sek Shir Cheong who taught me how to analyse sections of lung histology using the software Fiji, as well as how to use a range of scientific databases for genetic analysis.

The research we carried out was important in adding to the small number of studies that had previously investigated lung development in Down syndrome. In our study, we used a range of mouse models which all had three copies of different portions of chromosome 21. This allowed us to narrow down and identify the region of chromosome 21 that was critical in the development of the abnormalities found in the lung histology of these mouse models and the possible candidate genes causing them.

I was made to feel a part of the team as I attended weekly laboratory meetings with the group, which enabled me to keep up with and gain an understanding of the current research taking place at the lab. Additionally, observing presentations, as well as delivering some myself to the group, helped me to develop my presentation skills and allowed me to progress quicker as I received useful and regular feedback. I had a great time working at the lab, especially as I had not done any work like that before.”

– Onyinyechi

MSc project on ‘Investigating lung repair: a live imaging approach’

“My time in the Dean lab allowed me to develop a deeper understanding into how ideas are developed in the lab and how much collaboration is involved in research.” – Lauren

“For my master’s thesis I was lucky enough to undertake a 6-month research project with the dean lab. This experience was incredible, for the first time I was truly integrated into a labs’ research. For my project I was able to work with the on the Acid Injury Repair (AIR) model. This novel model uses hydrochloric acid to mimic lung injury and allows for the study of lung repair and regeneration. Working with Rosin Mongey, who established the AIR Model, I tested ways to image dynamic processes happening in the injured tissue.

Throughout my project I learnt new techniques and concepts. Thanks to the great supervision of Rosin and the FILM department, I became confident with microscopy, an area I knew little about. As microscopy is a central technique in biological research, these newly developed skills will help me in future research.

Alongside my lab work, I was invited to attend weekly lab and section meetings. These meetings helped to highlight the collaborative nature of research. In lab meetings I was kept up to date with the labs work and was able to present and receive feedback on my own, whilst in section meetings, I learnt about the research being performed by other groups.

My time in the Dean lab allowed me to develop a deeper understanding into how ideas are developed in the lab and how much collaboration is involved in research. I hope that the skills I have learnt during this project will help me in a future research career.”

– Lauren

Regenerative medicine goes main-stream

Walking through my local shopping centre the other week, I was surprised to see this new store that has just opened (see picture). It’s clear that ‘Regenerative Medicine’ is something the public responds favourably to. As a lab that conducts research aimed at identifying novel regenerative medicine treatments for lung disease, our hope is that funding agencies will be equally responsive to supporting research in this important area.

ERS monograph on Lung Stem Cells in Development, Health and Disease

The ERS has published a new monograph focused on lung stem cells.

This monograph from the European Respiratory Society (ERS) focuses on one of the most exciting areas of respiratory science- stem cells. The book covers the latest research and understanding about mouse and human lung stem cells and how they can be harnessed for therapeutic purposes.

A variety of experts in the field discuss how stem cells can be generated or stimulated from endogenous lung tissue. The book also contains several chapters on modelling lung and stem cell functions including a chapter on our own favourite model- precision-cut lung slices.

https://www.ersbookshop.com/lung-stem-cells-in-development-health-and-disease-669-p.asp

Congratulations Dr Róisín Mongey!

31st March 2021 – Massive congratulations to Róisín on a very successful PhD!

Róisín defended her thesis entitled ‘Investigating the role of vitamin A and retinoic acid signalling in lung homeostasis and repair’ and passed her viva without corrections! This coincided with the UK lockdown restriction easing and we were able to share a toast in a socially distanced manner on the beautiful Queen’s lawn.

ERS Lung Science Conference Best Poster Award 2021

Congratulations to Róisín, who was awarded the Best Poster Award at the European Respiratory Society Lung Science Conference 2021, for her work on “Investigating the role of vitamin A intake and retinoic acid signalling in lung homeostasis and repair- a multidisciplinary approach”. https://www.ersnet.org/events/lung-science-conference/

The conference was a great opportunity to interact with experts in the field and to learn about exciting new developments at the cutting edge of lung regenerative science.” – Róisín

“In March 2021 I won a bursary to attend the 19th European Respiratory Society Lung Science conference and present my work on ‘Investigating the role of vitamin A intake and retinoic acid signalling in lung homeostasis and repair- a multidisciplinary approach’. The presentation summarised key findings from my PhD: using dietary intake and genetic data from the large UK Biobank population to study the association between vitamin A intake, retinoic acid pathway genes and adult lung function in addition to lab-based work using our novel Acid Injury and Repair (AIR) model to study and manipulate RA signalling following lung injury. The presentations involved an online poster as well as 3 minute oral presentation followed by a stimulating discussion session. I thoroughly enjoyed the experience and was honoured to win the best poster award for my session.

As a recipient of a bursary award, I was also able to take part in the mentorship programme during which I received invaluable advice on my career progression from leaders in the field.

The organisers did an exceptional job putting together the conference programme despite the challenges of an online format. There were many exciting talks from leaders across the field of lung repair and regeneration. Topics covered cellular differentiation and interaction in the alveolar niche, exciting novel scaffolds to replicate and repair the lung and new in vitro and ex vivo models for the study of lung disease and repair to name a few. The conference was a great opportunity to interact with experts in the field and to learn about exciting new developments at the cutting edge of lung regenerative science.”

– Róisín

BTS Medical Student Award 2020

Congratulations to Ambreen, who was awarded the BTS Medical Student Award at the Winter Meeting 2020, for her work “Investigating the role of Daam2 in lung development”.
https://www.brit-thoracic.org.uk/about-us/news/2021/bts-medical-student-award-2020/

“With a burning curiosity about medical research, I wanted to carry out a lab experience to explore what this field entails.” – Ambreen

“During the summer of my second year at medical school, I was fortunate enough to spend some time working with the Dean lab, contributing to some work in investigating the role of a particular gene (dishevelled activator of morphogenesis 2 – Daam2) in lung embryogenesis. Working with Charlotte and the team was incredible, as I was able to carry out laboratory procedures we had been taught about in the early years of medical school and see, first-hand, the merits and challenges of a career in academia. 

To help support my time with the Dean lab, I applied for an Anatomical Society Undergraduate Summer Scholarship which I successfully received. As part of this award, I presented my work as a poster presentation at the Anatomical Society 2019 Winter meeting – my first conference!

I also presented by work at the British Thoracic Society’s 2020 Winter meeting and was very fortunate to receive the Medical Student Abstract award. This was a phenomenal experience, as despite a virtual conference, I was able to speak with inspirational clinical academics who further inspired me to explore the opportunities that clinical research has to offer.

My experience in the lab was critical in helping me to gain an insight into academia as a career and further fuelled my aspirations to get involved in research. I am currently completing my intercalated BSc at Imperial College London in Cancer Frontiers and look forward to pursuing a career in research alongside my clinical studies.”

– Ambreen

A breath of fresh ‘AIR’ in the study of lung repair and regeneration

A lung slice showing isolated areas of damaged (purple) and undamaged (yellow) tissue

 

Studying the mechanisms of lung repair and regeneration in the human lungs is challenging given their critical role. We have developed a new model, using slices of lung tissue, that can be used to study lung repair and regeneration. The Acid Injury and Repair (AIR) model works by using hydrochloric acid to injure a small part of the tissue slice whilst the surrounding area remains uninjured. This mimics the pattern of injury often observed in lung diseases. The AIR model enables tracking of different cell types, including stem cells as well as providing a platform to test potential new treatments to repair the lungs.

Researchers Sally Kim and Roisin Mongey worked on developing and validating this new tool which was recently published in Biomaterials. You can read about their work on the Imperial Faculty of medicine blog http://wwwf.imperial.ac.uk/blog/imperial-medicine/2021/01/13/a-breath-of-fresh-air-in-the-study-of-lung-repair-and-regeneration/

VANGL2 (Van Gogh-like 2): In Control of Mechanosignalling

Our new research article “The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling” has been published in Frontiers in Cell and Developmental Biology. 

In this study, Dr Sek Shir Cheong discovers how a mutation in the VANGL2 gene (Vangl2Lp), in mutant mice, interferes with normal mechanosignalling and directed cell migration which contribute to abnormal formation of alveoli, the site of gas exchange in the lungs. Mechanosignalling, “mechano-signalling”, simply put, is a signalling process induced by mechanical forces.

By monitoring in real time the movement of alveolar epithelial cells (an important cell type that form alveoli) in slices of lung tissue, we found that cells from the Vangl2Lp/+ mutant mice had slower and more restricted movement compared to cells from normal healthy mice. This resulted in fewer alveoli being formed, which reduces lung function in the mutant mice. To help us understand what causes the abnormal movement in these mutant cells, we isolated epithelial cells from the tracheas and lungs of Vangl2Lp/+ mutant mice, and labelled different components in the cells using antibodies. This process revealed that the Vangl2Lp mutation caused disruption of the actomyosin network (a kind of scaffold present in  cells that is analogous to the musculoskeletal system in the human body), as well as focal adhesions, which function as molecular clutches, enabling cells to attach to their surrounding matrix. In addition we found a reduction in key proteins responsible for mechanosignalling within the lung epithelial cells. All of these abnormalities leads to the the cells being floppy as they are unable to generate force, thereby affecting their ability to move or migrate which is particularly important during the process of lung formation or lung repair after injury. 

Lastly, we tested a drug WNT5A, a molecule that belongs to the same pathway as VANGL2, and showed that it could improve wound healing ability in the mutant cells, suggesting that WNT5A could be a potential target for lung repair. 

This article highlights a previously unkown role of VANGL2 in command and control of mechanosignalling.

 

Dr Bethany Taylor talks about her summer project in the Lung Development and Repair group and her Thorax publication

During my second year of medical school I decided that I wanted to gain some lab experience over Summer, as I realised medical research was an area I’d like to explore further. I was very fortunate to arrange to spend my Summer in the Dean lab and subsequently worked with Charlotte and Matt to design a project that would contribute to the labs work in investigating the mechanisms underlying Congenital Pulmonary Airway Malformation (CPAM). I applied for and gratefully received a Wellcome Student Scholarship to facilitate this, producing a report based on my findings. I found it a fantastic experience working within the research team and gained valuable insight into clinical academia through collaborating with clinicians at the Royal Brompton Hospital.

I have subsequently presented the results of my project at the 2019 Pathology Society Winter meeting held at the Royal Society of Medicine, and this year our article was published in BMJ Thorax. DOI: 10.1136/thoraxjnl-2020-214752.

My experience in the Dean lab has been integral to informing my choice to pursue academic research alongside my clinical work. I have since completed my BSc at Imperial in Cardiovascular Sciences, during which I conducted a lab project at Tokyo Medical and Dental University, and I am currently working as an academic foundation doctor in which I will complete my academic rotation in transplant and regeneration at Addenbrooke’s hospital, Cambridge.

Taylor B et al. Mechanism of lung development in the aetiology of adult congenital pulmonary airway malformations. Thorax 2020