Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Subject collections
    • Interviews
    • Sign up for alerts
  • About us
    • About DMM
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Outstanding paper prize
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contact
    • Contact DMM
    • Advertising
    • Feedback
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

User menu

  • Log in

Search

  • Advanced search
Disease Models & Mechanisms
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

supporting biologistsinspiring biology

Disease Models & Mechanisms

Advanced search

RSS   Twitter   Facebook   YouTube

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Subject collections
    • Interviews
    • Sign up for alerts
  • About us
    • About DMM
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Outstanding paper prize
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contact
    • Contact DMM
    • Advertising
    • Feedback
FIRST PERSON
First person – Emily Jones, Zoe Matthews and Lejla Gul
Disease Models & Mechanisms 2019 12: dmm039511 doi: 10.1242/dmm.039511 Published 18 March 2019
  • Article
  • Figures & tables
  • Info & metrics
  • PDF
Loading

ABSTRACT

First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Emily Jones, Zoe Matthews and Lejla Gul are co-first authors on ‘Integrative analysis of Paneth cell proteomic and transcriptomic data from intestinal organoids reveals functional processes dependent on autophagy’, published in DMM. Emily is a postdoctoral research scientist in the lab of Professor Simon Carding at Quadram Institute, Norwich, UK, investigating host-microbe interactions at the intestinal epithelial barrier. Zoe is a medical student (research completed during PhD) in the lab of Prof. Tom Wileman at Biomedical Research Centre, University of East Anglia, Norwich, UK, investigating stem cell biology, focussing on the small intestine. Lejla is a PhD student in the lab of Dr Tamas Korcsmaros at Earlham Institute, Norwich, UK, investigating the effects of environmental (e.g. microbes) and genetic factors on the human autophagy process.

Embedded Image

Emily Jones, Zoe Matthews and Lejla Gul

How would you explain the main findings of your paper to non-scientific family and friends?

EJ & ZM: Our work combined experimental biology and computational analysis. We started out in a lab, growing mini-guts (3D organoid cell cultures that mimic the intestine). We had two types of organoids: those that acted like a normal healthy small intestine and those that had an abnormality in a recycling protein (lack of the Atg16l1 gene). This deficient model is relevant to study Crohn's disease (CD), which is an inflammatory condition of the gastrointestinal tract, as patients suffering from CD have an altered form of this gene. We aimed to investigate the effect of Atg16l1 knockout on cellular functions using an organoid culture model.

LG: To prove our hypothesis, we developed a method combining both computational and experimental biology. We used this new pipeline to assess the effect of the Atg16l1 knockout, which causes autophagy impairment. Autophagy is a cellular degradation process targeting organelles, pathogens and specific proteins. We predicted the effect of protein-level changes due to autophagy impairment on cellular functional processes. We measured the quantity of proteins showing different abundances in organoids lacking the Atg16l1 gene, compared with wild types. Following data analysis, we identified functions that could have potentially been altered, and verified these experimentally.

What are the potential implications of these results for your field of research?

CD affects millions of people worldwide, but currently there is no cure for the disease. We have generated a Paneth-cell-enriched 3D organoid system to model the potential changes during the disease and discover the molecular background. We have implemented a bioinformatic pipeline to analyse systems-level changes in intestinal cells. As a result, potential functional changes related to CD were discovered, providing greater insight into the underlying mechanisms and aetiology of CD, and hopefully bringing research closer to an effective long-term treatment for patients.

“Potential functional changes related to CD were discovered, providing greater insight into the underlying mechanisms and aetiology of CD, and hopefully bringing research closer to an effective long-term treatment for patients.”

What are the main advantages and drawbacks of the model system you have used as it relates to the disease you are investigating?

Organoids grown from intestinal stem cells differentiate into all the cells of the intestinal epithelium, providing a useful laboratory model, both in terms of structure and function. Creating and using cell-type-specific enriched systems helps us to discover in vivo processes in an in vitro environment, thereby giving a nearly true insight into protein abundance changes in Paneth cells. The drawbacks of lineage-directing organoids into Paneth cells is that the final cultures are not pure – some stem cells remain, keeping the organoids alive. Also, here we have investigated a model system lacking the Atg16l1 gene, while in CD patients the ATG16L1 gene is in a mutated form. Therefore, the knockout model we used can be considered as an extreme model, where autophagy is impaired.

Figure1
  • Download figure
  • Open in new tab
  • Download powerpoint

Crypts of Lieberkühn from the mouse in vitro (left) and crypt from the in vitro organoid model (right).

“A surprising outcome of the work was how many collaborations were formed in order to combine experimental biology with computational biology.”

What has surprised you the most while conducting your research?

EJ & ZM: A surprising outcome of the work was how many collaborations were formed in order to combine experimental biology with computational biology. A large volume of data was generated by many research groups and it was exciting to see the project progress from the original samples produced in the laboratory.

LG: Based on the literature, autophagy and apoptosis generally show a negative correlation under most homeostatic conditions but, surprisingly, we found a positive correlation between the two processes. We assume that, when autophagy is impaired, the downregulation of apoptosis could prevent the perturbed Paneth cells from sacrificing themselves, which would then be compensated for by outcomes such as upregulation of DNA damage repair functions, as suggested previously.

Describe what you think is the most significant challenge impacting your research at this time and how will this be addressed over the next 10 years?

Our findings are based on a murine cell culture, so the next steps will be translating our pipeline for human samples, then verifying the results in the human system. As this is developed, we hope that it will lead towards a more specific understanding of the ATG16L1 mutation in CD, translating into clinical applications that provide more personalised, patient-specific treatment of CD. We are fortunate that Norwich Research Park continues to develop with the opening of the Quadram Institute, a state-of-the-art food and health research and endoscopy centre combining scientific excellence and clinical expertise, making this a more realistic goal over the next 10 years.

What changes do you think could improve the professional lives of early-career scientists?

EJ: I think it is important that early-career scientists are supported with longer-term projects that allow job security in order to enable them to publish their research and build their scientific career.

LG: The collaboration between different institutes and research groups is very important but one thing is more significant: collaboration among people from different areas of science. Early-career scientists should learn more about systems-level thinking using bioinformatics, outstepping the bounds of limited thinking.

What's next for you?

In the article, we focused mainly on the process of exocytosis when the protein turnover is disrupted in cells. Further experiments are needed to confirm the assumption about the role of DNA repair and apoptosis in Paneth cells and how the interruption of these processes could contribute to the pathogenesis of impaired autophagy-associated diseases such as CD. We look forward to testing our experimental-computational pipeline on patient-derived organoids.

Footnotes

  • Emily Jones's contact details: Quadram Institute, Norwich Research Park, Norwich, Norfolk NR4 7UA, UK. E-mail: emily.jones{at}quadram.ac.uk

    Zoe Matthews' contact details: Biomedical Research Centre, University of East Anglia, Norwich NR4 7TJ, UK. E-mail: z.matthews{at}uea.ac.uk

    Lejla Gul's contact details: Earlham Institute, Norwich Research Park Innovation Centre, Colney Lane, Norwich NR4 7UZ, UK. E-mail: Lejla.Gul{at}earlham.ac.uk

  • L.G. was supported by the BBSRC Norwich Research Park Biosciences Doctoral Training Partnership (grant BB/M011216/1).

  • © 2019. Published by The Company of Biologists Ltd
http://creativecommons.org/licenses/by/4.0

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Reference

  1. ↵
    1. Jones, E. J.,
    2. Matthews, Z. J.,
    3. Gul, L.,
    4. Sudhakar, P.,
    5. Treveil, A.,
    6. Divekar, D.,
    7. Buck, J.,
    8. Wrzesinski, T.,
    9. Jefferson, M.,
    10. Armstrong, S. D. et al.
    (2019). Integrative analysis of Paneth cell proteomic and transcriptomic data from intestinal organoids reveals functional processes dependent on autophagy. Dis. Model. Mech. 12, dmm037069. doi:10.1242/dmm.037069
    OpenUrlAbstract/FREE Full Text
Previous ArticleNext Article
Back to top
Previous ArticleNext Article

This Issue

RSSRSS

 Download PDF

Email

Thank you for your interest in spreading the word on Disease Models & Mechanisms.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
First person – Emily Jones, Zoe Matthews and Lejla Gul
(Your Name) has sent you a message from Disease Models & Mechanisms
(Your Name) thought you would like to see the Disease Models & Mechanisms web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
FIRST PERSON
First person – Emily Jones, Zoe Matthews and Lejla Gul
Disease Models & Mechanisms 2019 12: dmm039511 doi: 10.1242/dmm.039511 Published 18 March 2019
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
FIRST PERSON
First person – Emily Jones, Zoe Matthews and Lejla Gul
Disease Models & Mechanisms 2019 12: dmm039511 doi: 10.1242/dmm.039511 Published 18 March 2019

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts

Please log in to add an alert for this article.

Sign in to email alerts with your email address

Article navigation

  • Top
  • Article
    • ABSTRACT
    • Footnotes
    • Reference
  • Figures & tables
  • Info & metrics
  • PDF

Related articles

Cited by...

More in this TOC section

  • First person – Frederike Riemslagh
  • First person – Pranidhi Baddam
  • First person – Talia Nasr
Show more FIRST PERSON

Similar articles

Other journals from The Company of Biologists

Development

Journal of Cell Science

Journal of Experimental Biology

Biology Open

Advertisement

DMM and COVID-19

We are aware that the COVID-19 pandemic is having an unprecedented impact on researchers worldwide. The Editors of all The Company of Biologists’ journals have been considering ways in which we can alleviate concerns that members of our community may have around publishing activities during this time. Read about the actions we are taking at this time.

Please don’t hesitate to contact the Editorial Office if you have any questions or concerns.


Monica Justice bids farewell to DMM

In her farewell Editorial, outgoing Editor-in-Chief Monica Justice reminds us of the past half-decade of growth and of DMM's commitment to support the disease modelling community, concluding, “The knowledge and experience I gained during my time as Senior Editor and EiC at DMM is invaluable: working within a not-for-profit community publishing environment is a joy.”


3D imaging of beta cell mass in diabetic mouse models

In their inducible mouse model of diabetes, Roostalu et al. demonstrate how quantitative light-sheet imaging can capture changes in individual islets to help pharmacological research in diabetes.

Visit our YouTube channel to watch more videos from DMM, our sister journals and the Company.


Modelling Joubert syndrome patient-derived mutations in C. elegans

In this issue’s Editor’s choice, Karen Lange and colleagues used C. elegans to model and characterise two patient-derived mutations that cause the ciliopathy Joubert syndrome.


Interview – Karen Lange

First author of our current Editor’s choice, Karen Lange takes us behind the scenes of the paper, and shares her thoughts on how the lack of both time and job security will impact her research.

Articles

  • Accepted manuscripts
  • Issue in progress
  • Latest complete issue
  • Issue archive
  • Archive by article type
  • Subject collections
  • Interviews
  • Sign up for alerts

About us

  • About DMM
  • Editors and Board
  • Editor biographies
  • Travelling Fellowships
  • Grants and funding
  • Journal Meetings
  • Workshops
  • The Company of Biologists

For Authors

  • Submit a manuscript
  • Aims and scope
  • Presubmission enquiries
  • Article types
  • Manuscript preparation
  • Cover suggestions
  • Editorial process
  • Promoting your paper
  • Open Access
  • Biology Open transfer

Journal Info

  • Journal policies
  • Rights and permissions
  • Media policies
  • Reviewer guide
  • Sign up for alerts

Contact

  • Contact DMM
  • Advertising
  • Feedback

Twitter   YouTube   LinkedIn

© 2021   The Company of Biologists Ltd   Registered Charity 277992