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*Funded PhD Studentship Opportunity

Investigating targeted delivery of pro-repair factors to the lungs

About the Project

3-year NHLI-funded PhD post-starting Spring 2023

Summary of Research

Applications are invited from candidates with a Masters degree and undergraduate training in a biological science or bioengineering discipline for a PhD to investigate targeted delivery of pro-repair factors to the lungs.

The studentship will be funded for three years with a tax-free bursary of £19,668 per annum plus tuition fees. This studentship is based in the National Heart and Lung Institute at Imperial College London and will be supervised by Dr Charlotte Dean and Dr Matthew Hind.

The lungs are capable of intrinsic repair however, in some people, disruption of these repair processes leads to disease caused either by lack of repair, or an overactive repair response. There are no curative treatments available for many prominent lung diseases including Chronic Obstructive Pulmonary Disease, Adult Respiratory Distress Syndrome and Bronchopulmonary Dysplasia.

Regenerative biology now offers real therapeutic potential to repair or regrow damaged lungs. The aim of the lung development and repair group is to identify and develop regenerative medicine treatments for the lungs that can be used to repair damaged lung tissue and ameliorate diseases.

This PhD project will investigate strategies to target delivery of pro-repair treatments to the lungs. The student will investigate methods to encapsulate pro-repair factors in nanoparticles or hydrogels to extend the efficacy of the pro-repair signals and allow their precise targeting to the lung alveoli. The project will utilise a variety of cutting-edge models, including 3D lung slices to investigate ways to combine potential repair treatments with bioengineering approaches to stimulate optimal lung repair.

The student will be based in the Cardio-Respiratory Section within the National Heart and Lung Institute, which provides an exciting environment, with state of the art facilities and excellent opportunities for PhD student training including research seminars. All students will belong to Imperial’s award-winning Graduate School which provides a comprehensive Professional Skills Programme.

How to Apply

Applicants must hold, or expect to obtain, a first or upper second-class undergraduate degree or UK equivalent, along with a Masters, both in an appropriate subject from a recognised academic institution.

To apply please email the following information to c.dean@imperial.ac.uk with:

  • Curriculum Vitae (max 2 pages)
  • Personal statement (1 page)
  • Name, address, telephone number or email of two referees. At least one of which must be academic.

Applicants unable to attend interview in person will undergo an online interview and be invited for a second face-to-face meeting before confirmation of offer.

Eligibility and funding notes

This studentship is open to home and international students

The successful candidate will receive a bursary of £19,668 per annum plus tuition fees for home students. Successful non-UK students will be offered a bursary with a contribution of £20,000 p.a. towards international tuition fees and will be expected to cover the remaining fees themselves.

Please note that candidates must fulfil College admissions criteria.

Application deadline: 30th November 2022

Funding to investigate the capacity of Wnt5a to repair damaged lungs

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.

NHLI Research Away Day 2022

NHLI Research Away Day 2022 at the Queen Elizabeth II Conference Centre, London.

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.

The Frontiers Editor’s Pick with our article is now published as an e-book

The “Editor’s Pick 2021: Highlights in Cell Adhesion and Migration” collection by the Frontiers in Cell and Developmental Biology that includes our article ‘The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling’ is now available as an e-book!

A comprehensive summary of the findings and impacts of our study by the Frontiers editors can be found on Page 7 in the e-book. To read the full article, go to Page 128-146.

Our article has been selected as Editor’s Pick!

(Left) Live imaging of Vangl2Lp postnatal day 3 precision-cut lung slice to assess epithelial cell migration. (Middle and right) Striking anomalies in focal adhesions (green) and F-actin (magenta) in mutant epithelial cells (right) compared to wild type cells (middle).

Our recent article ‘The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignalingpublished in Frontiers in Cell and Developmental Biology has been selected to be featured in the collection “Editor’s Pick 2021: Highlights in Cell Adhesion and Migration”.

https://www.frontiersin.org/research-topics/30228/editors-pick-2021-highlights-in-cell-adhesion-and-migration#articles

This article highlights a previously unknown function of the core planar cell polarity (PCP) protein, VANGL2, in control of mechanosignalling and we propose this underlies the key role of the PCP pathway in tissue morphogenesis and repair.

We employed a combination of live imaging of ex vivo 3D precision-cut lung slices, in vitro 2D cell culture and functional assays to show that disrupted epithelial cell migration in Vangl2Lp (Looptail) mutant mice was caused by underlying aberrant cell mechanics. Our findings were further consolidated by the use of sophisticated elastic micropillar arrays that demonstrated abnormal cellular traction force in epithelial cells from Looptail mutant mice (collaboration with Dr Armando del Río Hernández, ICL Department of Bioengineering).

Click the link below for more details about this study:

The full article can be found here :

https://www.frontiersin.org/articles/10.3389/fcell.2020.577201/full

New Chapter for Róisín

After 4 years in the lab, Róisín is off to begin a new role training to be a Clinical Trials manager at Medpace. Róisín came to the lab as a Master’s student and was subsequently awarded a PhD to study the role of retinoic acid in lung repair. After completing her PhD in early 2021, Róisín stayed on for a year as a post-doc. During her time in the lab Róisín worked to establish a novel model of lung injury and repair (Kim-Mongey et al. 2021 Biomaterials) which she then used to investigate the role of retinoic acid. In addition, Róisín has shown an important role for dietary vitamin A intake on lung function through large-scale population studies (collaboration with Dr Cosetta Minelli).

We wish Róisín every success in her new role!

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