Example projects and silo switches

The Wellcome Trust 4-year PhD in Immuno-Matrix in Complex Disease programme enables trainees to undertake a range of PhD projects at the interface of matrix biology, immunology and complex disease.

You will also have the opportunity to experience alternative careers related to your chosen project through silo switches, where you can carry out research in a discipline distinct from your laboratory project to include in your thesis.

Examples of current and past projects and silo switches can be found below.

Examples of projects and related silo switches


Project: Regulation of skin inflammation by extracellular matrix.
Primary supervisor: Amy Saunders
Co-supervisor: Doug Dyer
Silo switch: Manchester Institute of Health & Performance: Physical therapy procedures to reverse adhesions related injury.

Project: The role of dendritic cells in directing fibrosis during helminth infection.
Primary supervisor: Andrew MacDonald.
Co-supervisor: Judi Allen.
Silo switch: MRC/UVRI Uganda: Research Unit: Approaches and Issues of Helminth infection in Uganda*.

Project: Targeting macrophages to prevent fibrosis and surgical adhesions.
Primary supervisor: Dominik Ruckerl
Co-supervisor: Tim Illidge
Silo switch: Manchester Institute of Health & Performance: Physical therapy procedures to reverse adhesions related injury.

Project: The role of uterine macrophage-ECM crosstalk in reproductive disease.
Primary supervisor: Elizabeth Mann
Co-supervisor: Judi Allen
Silo switch: Manchester University Foundation Trust: Stratification of patients with disorders of the reproductive tract.

Project: How does matrix control inflammasome activation in macrophages.
Primary supervisor: Gloria Lopez-Castejon
Co-supervisor: Pawel Paszek
Silo switch: Dept of Mathematics: Modelling of inflammasome activation hubs.

Project: Immune-matrix interactions supporting rapid oral wound healing.
Primary supervisor: Joanne Konkel
Co-supervisor: Rachel Lennon
Silo switch: Health Innovation Manchester: Oral health and socioeconomics.

Project: Effects of monocyte priming on matrix-remodelling during gastrointestinal inflammation.
Primary supervisor: John Grainger
Co-supervisor: Pat Caswell
Silo switch: GSK: Bioinformatic approaches to repurpose drugs that modify macrophage/stromal cell interactions.

Project: How microglial cell homeostasis is controlled by the extracellular matrix during health and disease.
Primary supervisor: Kevin Couper
Co-supervisor: Tony Day
Silo switch: Salford Royal infirmary brain bank.

Project: Complex interactions of innate lymphoid cells within the intestinal microenvironment in health and IBD.
Primary supervisor: Matt Hepworth
Co-supervisor: Martin Humphries
Silo switch: Manchester Gastroenterology/eHealth: Co-morbidities with inflammatory bowel disease (IBD).

Project: Decoding outcomes of host-pathogen interactions via single cell NF-kB dynamics
Primary supervisor: Pawel Paszek 
Co-supervisor: Elaine Bignell
Silo switch: Mark Muldoon (School of Mathematics): Deterministic and stochastic modelling of the NF-kB system.

Project: Defining extracellular matrix function during intestinal helminth infection.
Primary supervisor: Richard Grencis
Co-supervisor: Tony Day
Silo switch: MRC/UVRI Uganda Research Unit: Approaches and Issues of Helminth infection in Uganda*.

Project: Mast Cells regulation in the remodelled lung.
Primary supervisor: Silvia Bulfone Paus
Co-supervisor: Tracy Hussell
Silo switch: Asthma / Allergy charity public engagement experience.

Project: Extracellular matrix changes shape immune cell functions during allergic airway inflammation.
Primary supervisor: Tara Sutherland
Co-supervisor: Karl Kadler
Silo switch: University Hospital of South Manchester: The use of continuous positive airway pressure sleep apnoea.

Project: The impact of hypertension on cell positioning and retention in the lung during inflammation.
Primary supervisor: Tracy Hussell
Co-supervisor: Peter Cook
Silo switch: Division of Informatics, Imaging & Data Sciences. Examining electronic health records for the combined hypertension with asthma disease cluster.

Matrix biology

Project: Immune-driven changes in the microbiota and mucus landscape during parasite infection.
Primary supervisor: Dave Thornton
Co-supervisor: Richard Grencis
Silo switch: Professor Chris Evans, University of Colorado, USA, Novel transgenic models.

Project: Circadian rhythm in immune and stromal cells during wound healing.
Primary supervisor: Karl Kadler
Co-supervisor: Tracy Hussell
Silo switch: Wound healing with zebrafish as a model organism. Paul Martin, University of Bristol.

Project: Immune cell adhesion. signalling in the tumour stroma.
Primary supervisor: Martin Humphries
Co-supervisor: Dan Davis
Silo switch: University of Ghent: Bioinformatic analysis of proteomic data from isolated integrin adhesion complexes.

Inflammatory cytokines in shaping the metastatic matrix niche.
Co-supervisor: Pat Caswell
Co-supervisor: Santiago Zelenay
Silo Switch: TBC

Project: Linking basement membrane biology to human disease.
Primary supervisor: Rachel Lennon
Co-supervisor: Sebastian Viatte
Silo switch: David Sherwood Duke University: Basement membrane biology in C. elegans.

Project: Immuno-matrix; inflammation and inflammatory disease; proteoglycans; glycosaminoglycan-protein interactions
Primary supervisor: Tony Day
Co-supervisor: TBC
Silo switch: TBC

Project: Circadian clock regulation of mucin matrix biology and gut immunity
Primary supervisor: Qing-Jun Meng
Co-supervisor: Dave Thornton
Silo switch: Laboratory of Biological Rhythms of the Czech Academy of Sciences, Prague

Complex disease (including cancer)

Project: Early life risk factors for asthma and allergies.
Primary supervisor: Angela Simpson
Co-supervisor: Silvia Bulfone Paus
Silo switch: Manchester University NHS Foundation Trust: Audit in Respiratory clinic.

Project: The effect of co-morbidity on the glycocalyx in brain disease.
Primary supervisor: Catherine Lawrence
Co-supervisor: Douglas Dyer
Silo switch: Secondment to the Stroke Association.

Project: Influence of matrix on microglia pattern recognition receptor signalling.
Primary supervisor: David Brough
Co-supervisor: Catherine Lawrence
Silo switch: University of Freiburg: Matrix link to neurodegeneration.

Project: Epithelial cell:dendritic cell:matrix crosstalk during chronic fungal pulmonary disease.
Primary supervisor: Elaine Bignell
Co-supervisor: Andrew MacDonald
Silo switch: National Aspergillosis Centre, Manchester.

Project: The role of the matrix in regulating human regulatory T cell function in the inflamed gut.
Primary supervisor: Graham Lord
Co-supervisor: Rachel Lennon
Silo switch: Clinical experience.

Project: The extracellular matrix in the dual role of inflammation in cancer.
Primary supervisor: Santiago Zelaney
Co-supervisor: Judi Allen
Silo switch: TBC

Project: Characterising B cells in Rheumatoid Arthritis: Their role in susceptibility, pathogenesis, and treatment response.
Primary supervisor: Sebastien Viatte
Co-supervisor: John Grainger
Silo switch: Harvard Medical School, Boston: Bioinformatics techniques for the analysis of multidimensional datasets in immunology.

Project: How immune responses and extracellular matrix respond to radiotherapy.
Primary supervisor: Tim Illidge
Co-supervisor: Mark Travis
Silo switch: Christie Hospital: Involvement in cancer clinical trials.


Project: Chemokine and glycocalyx collaboration during leukocyte recruitment in health and disease.
Primary supervisor: Douglas Dyer
Co-supervisor: Catherine Lawrence
Silo switch: MedImmune/AZ: Immunotherapeutics.

Project: Cytokine regulation of collagen turnover and deposition.
Primary supervisor: Judi Allen
Co-supervisor: Karl Kadler
Silo switch: Joe Swift Biomechanics UoM: Impact of tissue stiffness on immune cell function.

Project: B cell and matrix interactions in tissue repair.
Primary supervisor: Kathryn Else
Co-supervisor: Sebastian Viatte abd Madhvi Menon
Silo switch: Faculty of Science and Engineering: Biomaterial modulation of matrix.

Project: How does cross-talk between mucus and the immune system control immune responses to maintain health and fight infection?
Primary supervisor: Mark Travis
Co-supervisor: Dave Thornton
Silo switch: Manchester University NHS Foundation Trust: Characteristics of mucus from patients with inflammatory disorders.

Current PhD projects

Lung extracellular matrix remodelling in asthma

Full project title: Investigating the influence of immune cells and mediators on lung extracellular matrix remodelling during asthma
PhD researcher: Hannah Tompkins
Supervisors: Dr Tara Sutherland
Co-supervisors: Professor Andrew MacDonald and Professor Karl Kadler

Asthma is a chronic inflammatory disorder of the lungs which causes the airways to temporarily narrow in response to specific triggers. Narrowing can usually be relieved using an inhaler, but there are multiple long term impacts of asthma.

Alongside chronic inflammation, asthma is also characterised by airway remodelling. Airway remodelling is a process whereby structural tissue cells make excessive matrix proteins (e.g. collagen) leaving the lung stiff, less elastic and with reduced function.

Current treatments fail to reverse/prevent these structural lung changes from occurring in asthma. I aim to learn more about lung remodelling in asthma and how it is regulated. Initially, I will investigate the different types of matrix changes in the lungs tissue from people with asthma and see whether any changes are associated with any specific types of inflammation.

I will also use a mouse model of airway remodelling to examine how remodelling is initiated and whether inhibiting inflammation or specific molecules that are increased in asthma, prevents remodelling from developing.

Overall, this project will help us understand how the matrix changes in the lungs during remodelling and will help identify the cells or molecules that could be targeted therapeutically to prevent or reverse lung remodelling in asthma.

The extracellular matrix in psoriasis-like skin inflammation

Full project title: The role of the extracellular matrix in the initiation and resolution of psoriasis-like skin inflammation
PhD researcher: Megan Priestley
Supervisor: Dr Amy Saunders
Co-supervisors: Dr Douglas Dyer, Professor Rachel Lennon

Psoriasis is a skin disease linked to increased numbers of immune cells entering the skin from the blood and causing inflammation in the skin.

The components of the blood vessel wall can limit the numbers of immune cells which can migrate across it and into the skin. The glycocalyx is a layer of sugars and proteins lining this wall and acts as a barrier against immune cell migration, being broken down in some types of inflammation to allow more cells across.

Another part of this wall is the basement membrane, a layer of proteins which can also limit immune cell migration. The roles of these components in the blood vessels have not previously been investigated in psoriasis.

This project will examine their make-up in healthy versus psoriasis skin and will manipulate them to see how this affects immune cell recruitment. When psoriasis resolves, there is a 'blush' left in skin where the lesions were and, when another flare-up occurs, it happens in these exact same areas.

This suggests that the skin never fully resolves after psoriasis and that these areas are primed for inflammation. This project will also examine these components in resolved skin and attempt to re-initiate psoriasis here.

Chitinase-like proteins as regulators

Full project title: The function of chitinase-like proteins as regulators of the immune system and the extra-cellular matrix using models of helminth infection
PhD researcher: Georgia Baldwin
Supervisors: Professor Judi Allen
Co-supervisors: Professor Tony Day

The chitinase-like proteins (CLPs) evolved from enzymes known as chitinases that are produced by mammals, as well as plants and bacteria, to break down chitin, which is very abundant in nature and potentially pathogenic.

The CLPs are immune proteins that are known to be biomarkers for poor prognosis in numerous diseases. They are constitutively expressed as well as upregulated during a type 2 immune response to parasitic challenge or allergy.

Binding to molecules in the extra-cellular matrix, the network surrounding cells is a known feature of this group, and a role in tissue repair, as well as host defence, has been implicated.

However, exact function and mechanism of action remains ill-defined. Using models of parasitic worm infection to create a type 2 immune environment, and using mice with gene deletions who lack production of these proteins, I aim to define their function and mechanisms of action and their regulation of each other.

This knowledge could lead to the ability to manipulate the CLPs to have a positive effect on wound healing and tissue repair, particularly during chronic disease where fibrosis - the irreversible scarring of organs - can compromise function and often be fatal.

Lymphoid cell-stromal interactions

Full project title: Dissecting innate lymphoid cell-stromal interactions in extracellular matrix remodelling and immunity
PhD researcher:
Rachel Finlay
Supervisors: Dr Matthew Hepworth
Co-supervisors: Dr Tara Sutherland and Professor Karl Kadler

Innate lymphoid cells are rare immune cells enriched in barrier tissues such as the gut or lung, and within lymph nodes, that play a key role in regulating immune responses. Furthermore, innate lymphoid cells localise to specific places within these tissues.

While some of the interactions that occur between ILCs and other cells in the same place are understood, the localisation of ILCs and how this changes throughout the course of infection is not very well understood.

Therefore, to better define how ILCs communicate with other cells and what signals are involved in regulating their localisation, both in health and disease, I will firstly use bioinformatic tools to assess whether there are novel cell-cell interactions between ILCs and other cells. I will then image ILCs over the time-course of an infection using imaging mass cytometry.

This work will help us understand how ILCs communicate with other cells and give new insights into cues that regulate ILC localisation in both health and throughout infection and, in turn, how ILCs modulate the adaptive and innate immune response.

Immune cells in extracellular matrix homeostasis

Full project title: Understanding the role of immune cells in extracellular matrix homeostasis in health and disease
PhD researcher: Katherine Lowles
Supervisor: Professor Karl Kadler
Co-supervisors: Professor Tracy Hussell and Professor Mark Travis

Dysregulation of the extracellular matrix (ECM) drives chronic diseases including osteoarthritis, fibrosis and cancer. Processes leading to dysregulation remain to be fully elucidated, though evidence shows that both the circadian clock and immune cells are involved in ECM deposition and turnover.

My PhD will focus on collagen, the predominant component of the ECM. Collagen is believed to be secreted via two pathways; the first pathway is clock-independent. The second is circadian clock-regulated, and leads to collagen fibril formation.

As an overproduction of collagen fibrils is the hallmark of conditions such as fibrosis, we will investigate how immune cells and the circadian clock influence collagen secretory pathways. We will determine how clock-altering cross talk between immune cells and tissue-resident fibroblasts alters collagen synthesis and deposition using co-cultures of immune cells with fibroblasts expressing NanoLuciferase-procollagen.

We will identify circadian clock-controlled proteins (CCCPs) using mass spectrometry tools. We will then use light microscopy to image matrix assembly in CRISPR-Cas9 edited cells that are deficient in or constitutively expressing the identified CCCPs.

This work will provide insight into collagen regulation and how the collagen secretory pathways can be subverted for therapeutic benefit.

Tumour microenvironment and cell-matrix interactions in glioblastoma

Full project title: High dimensional spatial analysis of the tumour microenvironment and cell-matrix interactions that drive tumour progression, resistance and recurrence in glioblastoma
PhD researcher: Leoma Bere
Supervisors: Dr Kevin Couper
Co-supervisors: Professor David Brough and Professor Anthony Day

Glioblastomas are the most aggressive and lethal brain tumours with average survival of less than 14 months, despite maximal treatment encompassing surgical removal and simultaneous radio- and chemotherapy.

Glioblastomas are complex tumours, with the tumour tissue (referred to as the tumour microenvironment [TME]) comprised of many types of cells including tumour cells, brain cells and immune cells.

Importantly, the TME is not homogenous throughout glioblastomas and frequently forms different regions, which have different biological characteristics. The relative impact of different TME regions on the clinical outcome of GBM is still poorly understood.

In this project, I propose to spatially map how different populations of tumour cells, immune cells (focussing on a population called myeloid cells) and the extracellular matrix (the scaffold that holds tissues together) interact within different regions of the glioblastoma TME.

By comparing these features within glioblastoma samples obtained from different patients following surgical resection, I will thus identify the key features that determine glioblastoma treatment resistance and the speed of post-surgical recurrence. 

My project will highlight new avenues for therapy for glioblastoma, which I will test within in vivo models of glioblastoma.

NK cell activating receptor signalling at immune-tumour synapse

Full project title: Mechanisms of NK cell activating receptor signalling at immune-tumour synapse and how it synergises with integrin signalling
PhD researcher: William Zammit
Supervisor: Professor Martin Humphries
Co-supervisors: Professor Daniel Davis

Natural killer (NK) cells play a key role in our first line of defence against cancer and infectious diseases. NK cells achieve this through activating and inhibitory receptors that survey proteins on nearby cells through the formation of an immune synapse.

Healthy cells express surface proteins that bind to inhibitory receptors and dampen the activating signals, whereas abnormal cells have either too many activating signals or too few inhibitory signals, which results in their killing by NK cells. Adhesion receptors, known as integrins, synergise with NK cell receptors and cytoskeletal proteins to form the immune synapse and subsequent NK cell killing.

I aim to gain a greater insight into the activating receptor, NKG2D. I will do this using an approach known as proximity labelling (PL).

I will fuse labels onto proteins of interest (baits) and, in specific conditions, these baits will label nearby proteins (prey). Using mass spectrometry, the prey will then be identified and validated for function.

The application of PL on NKG2D can help uncover new protein associations (both signalling proteins and receptors) and provide insight into its link with adhesion signalling. This can inform future therapeutic targeting strategies or even discover novel targets for future cancer treatments.