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Fully funded 3 year PhD Studentship – 3D patient-derived models of the human intestinal tract to study inflammation and impact of cryopreservation, storage and transportation.


   Wellcome-MRC Cambridge Stem Cell Institute

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  Dr M Zilbauer, Dr R Owens  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

A PhD scholarship is available (subject to contract) for this three-year project to be completed in collaboration with Cytiva beginning January 2023.

Key words: Organoids, 3D models, Intestinal epithelium, cryopreservation

PROJECT:

This project will use engineered 3D models of the intestinal tract with integrated multi-parametric readouts to understand interactions between important components of tissue of the intestinal tract, in the context of inflammation. We will develop novel co-culture organoid systems to investigate the cross talk between the human intestinal epithelium with immune cells, and microbial cells representing the microbiome.

The aims of the project are as follows:

  1. Integrate human organoids with 3D intestinal models
  2. Characterise models for immune and microbiome crosstalk
  3. Investigate organoids from different gut segments and from patients of different age (foetal, paediatric, adult) in the context of inflammation and IBD
  4. To test the suitability of cryopreservation techniques/reagents to be used for a. Intestinal organoids (and/or co-cultures) and b. Primary gut tissue (to allow generation of organoids)
  5. To test the suitability of alternative techniques for tissue dissociation to generate high quality organoid cultures

ENVIRONMENT:

Prof Zilbauer’s group has extensive experience in the establishment, differentiation and gene editing of human intestinal organoids. Prof Owens’ group has extensive expertise in development of 3D models with integrated fluidics and electronics.

This studentship will be in collaboration with the University of Cambridge and Cytiva, Global Lifesciences Operations Ltd (Histon, Cambridge). It is anticipated that the student will divide their time at the University lab (based at Stem cell Institute) and Innovation Hub (iHub) according to the guidelines of the studentship contract. However, it is expected that the student will manage the time in both labs according to the demand of the ongoing experiments. The student will take full advantage of the newly expanded cryobiology and cell biology labs at the iHub on the Cambridge site and will have opportunities to interact and collaborate with our UK and European manufacturing centres.

TEAM WORK:

The student will join a diverse, supportive and friendly team of scientists, clinicians and other professionals within the Stem Cell Institute, the Dept. of Chemical Engineering and Biotechnology and at Cytiva iHub. We place major emphasis on the importance of team work and an enjoyable work environment as a foundation for performing internationally leading translational research. This will allow the student to acquire cutting edge research methodologies in a supportive environment, where they can focus on making the best possible scientific progress. As a graduate student at Cambridge you will have access to a wide range of training opportunities and benefit from close supervision provided by a primary and secondary PhD supervisor as well as a personal mentor.

CANDIDATE: The successful candidate is expected to have (or expect to obtain by the start date) at least an upper second-class honours degree (or equivalent) in a relevant subject.

In summary, this PhD program offers the unique opportunity to work at the interface of basic science and clinical medicine aiming to train independent, innovative scientists capable of perusing translational research using cutting edge technology. Training will include both laboratory based molecular biological methods as well as bioinformatic skills allowing analysis of large data sets.

The post requires someone who is enthusiastic, focused, and has a passion for cutting edge science. The successful candidate will play a crucial part in leading aspects of our research theme and will be expected to strengthen existing collaborations as well as developing new ones.

HOW TO APPLY

To apply online for this vacancy and to view further information about the role, please visit:

https://www.postgraduate.study.cam.ac.uk/courses/directory/blscpdscp 

Applicants should refer to Dr Matthias Zilbauer and Prof Roisin Owens in the ‘proposed supervisor’ section of the application form.

The closing date for applications is 04th Oct 2022. The interview date expected in the October 2022.

STUDENT SUPPORT AND TRAINING

Cambridge Stem Cell Institute is a world-leading centre for stem cell research with a mission to transform human health through a deep understanding of stem cell biology. Our scientists study stem cell behaviour, both normal and pathological, and use their findings to improve the prevention, diagnosis and treatment of diseases. The Institute consists of 28 outstanding research groups, working across three key research themes: Stem Cell States, Stem Cells in Disease and Stem Cells & Therapeutics.

During their PhD, students are based in a research group, supported by their primary supervisor and the Institute's Postgraduate Education Committee and Postgraduate Student Committee. There is no taught or examined coursework, but students are encouraged to attend the wide variety of lectures and training courses available to them across the Institute and wider University. This includes a centrally-run Statistics course and the University Core Skills Training Programme, which includes sessions on Time Management, Presentation and Performance and Scientific Writing. Students at the Institute will be members of the University’s Postgraduate School of Life Sciences (PSLS) who offer a wide variety of core skills and professional development training. Visit the Researcher Development page on the PSLS website for more information. In addition, the student can also take advantage of training courses and seminars in therapeutic sciences offered by Cambridge Academy of Therapeutic Sciences.

All first year postgraduate students at the Institute are encouraged to participate in the 'Stem Cell Discussion Course' which occurs weekly during term-time. There will also be essential induction training including various safety inductions, and facility introductory courses on Imaging, Flow Cytometry and Bioinformatics.

All students are expected to attend all internal and external seminars held within the Jeffrey Cheah Biomedical Centre, including the 'Research Culture and Integrity' seminar series. Institute Staff and Students are also encouraged to attend the various research seminars, talks and workshops held across the Biomedical Research Campus and elsewhere within the University.


Funding Notes

Applications from prospective students are invited for a fully funded PhD studentship under the joint supervision of Dr Matthias Zilbauer, (Stem Cell Institute, University of Cambridge) and Prof Roisin Owens (Dept. of Chemical Engineering and Biotechnology, University of Cambridge UK).
The studentship will cover tuition and college fees as well as maintenance grant. Owing to funding restrictions, the studentship is only available at home fees rate.

References

Key publications:
1. Elmentaite R, Kumasaka N, Roberts K, Fleming A, Dann E, King HW, Kleshchevnikov V, Dabrowska M, Pritchard S, Bolt L, Vieira SF, Mamanova L, Huang N, Perrone F, Goh Kai'En I, Lisgo SN, Katan M, Leonard S, Oliver TRW, Hook CE, Nayak K, Campos LS, Domínguez Conde C, Stephenson E, Engelbert J, Botting RA, Polanski K, van Dongen S, Patel M, Morgan MD, Marioni JC, Bayraktar OA, Meyer KB, He X, Barker RA, Uhlig HH, Mahbubani KT, Saeb-Parsy K, Zilbauer M, Clatworthy MR, Haniffa M, James KR, Teichmann SA. Cells of the human intestinal tract mapped across space and time. Nature. 2021 Sep;597(7875):250-255. doi: 10.1038/s41586-021-03852-1. Epub 2021 Sep 8.
2. Elmentaite R, Ross ADB, Roberts K, James KR, Ortmann D, Gomes T, Nayak K, Tuck L, Pritchard S, Bayraktar OA, Heuschkel R, Vallier L, Teichmann SA, Zilbauer M. Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn's Disease. Dev Cell. 2020 Dec 21;55(6):771-783.e5. doi: 10.1016/j.devcel.2020.11.010. Epub 2020 Dec 7.
3. Howell KJ, Kraiczy J, Nayak KM, Gasparetto M, Ross A, Lee C, Mak TN, Koo BK, Kumar N, Lawley T, Sinha A, Rosenstiel P, Heuschkel R, Stegle O, Zilbauer M. DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With Outcome. Gastroenterology. 2018 Feb;154(3):585-598. doi: 10.1053/j.gastro.2017.10.007. Epub 2017 Oct 12.
4. Kraiczy J, Nayak KM, Howell KJ, Ross A, Forbester J, Salvestrini C, Mustata R, Perkins S, Andersson-Rolf A, Leenen E, Liebert A, Vallier L, Rosenstiel PC, Stegle O, Dougan G, Heuschkel R, Koo BK, Zilbauer M. DNA methylation defines regional identity of human intestinal epithelial organoids and undergoes dynamic changes during development. Gut. 2019 Jan;68(1):49-61. doi: 10.1136/gutjnl-2017-314817. Epub 2017 Nov 15.
5. C-M. Moysidou, A.M. Withers, A.J. Nisbet, D.R.G. Price, C.E. Bryant, C. Cantacessi, R.M. Owens. “Investigation of Host–Microbe–Parasite Interactions in an In Vitro 3D Model of the Vertebrate Gut”. 2022 Adv Biology. https://doi.org/10.1002/adbi.202200015
6. C. Pitsalidis, A-M. Pappa, A.J Boys, Y. Fu, C-M. Moysidou, D. van Niekerk, J. Saez, A. Savva, D. Iandolo, R.M. Owens. “Organic Bioelectronics for In Vitro Systems”. Chemical Reviews, 2022 https://doi.org/10.1021/acs.chemrev.1c00539
7. C-M. Moysidou, C Barberio, R.M. Owens, “Advances in Engineering Human Tissue Models”. Frontiers in Bioengineering and Biotechnology 8, 1566 2020https://doi.org/10.3389/fbioe.2020.620962
8. C-M. Moysidou, C. Pitsalidis, M Al-Sharabi, A.M. Withers, J.A. Zeitler, R. M. Owens. A 3D bioelectronic model of the human intestine”. Advanced Biology https://doi.org/10.1002/adbi.202000306
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