Underpinning Bioscience

Xenopus tropicalis tadpoles and egg expressing deferent Fluorescent proteins; Prof Amaya utilises this organism as a model for wound healing, as tadpoles have the ability to regenerate amputated tails. Image courtesy of Prof. E Amaya.

Underpinning Bioscience

We are associated with basic researchers who work towards understanding the fundamental mechanisms of tissue repair and regeneration.

Molecular and Cellular Biology

Professor Enrique Amaya

Professor of Tissue Regeneration
Faculty of Biology, Medicine and Health
enrique.amaya@manchester.ac.uk
Professor Amaya’s University Profile

The Molecular and Cellular Basis of Tissue Repair and Regeneration

In order to identify new genes involved in wound healing, Professor Amaya’s group plan to perform large-scale screens aimed at identifying genes, which either promote or delay healing in embryos. In addition, they have begun to investigate the development of primitive myeloid cells in Xenopus and have been studying their role during embryonic wound healing. Finally, Xenopus tadpoles are able to regenerate all the tissues in the tail, following amputation, within nine days. They are using functional genomic approaches to identify novel genes involved in the regeneration of all the tissue types in the tail, which include the vasculature, muscle, spinal cord and the notochord. The ultimate aim of this work is to identify new gene targets, which may form the basis of novel therapeutic and clinical applications to wound healing and tissue regeneration.

Dr Karel Dorey

Lecturer
Faculty of Biology, Medicine and Health
karel.dorey@manchester.ac.uk
Dr Dorey’s University Profile

The Role of Growth Factor Signalling During Development and Regeneration

The Dorey Lab aims to understand how Receptors Tyrosine Kinases (RTKs) can elicit a precise cellular response in the complex environment of the organism. To this end, they are investigating the molecular mechanisms controlling the activity of intracellular signalling pathways downstream of RTKs during Xenopus development. They are particularly interested in the role of RTK signalling during gastrulation, during neural development and maturation. These are two very different systems, allowing them to ask complementary questions about the mechanisms of action of RTKs during embryonic development. During gastrulation, Fibroblast Growth Factor (FGF) plays an essential role for two very important developmental events: mesoderm specification and morphogenetic movements. Gastrulation is therefore a relatively simple model to study how the same signal (FGF) is interpreted differently by mesodermic cells.

During motor neurons (MNs) development, they have recently reported that another RTK (TrkB and its ligand BDNF) has a crucial role in regulating axonal branching (Panagiotaki et al. 2011). Whilst axonal branching plays an essential role in allowing the formation, refinement, and maintenance of functional neural circuits, the mechanisms regulating branching are poorly understood. Their work places them in a unique position to elucidate how RTK signalling controls cell shape (or “unicellular morphogenesis”). In the longer term, they aim to use this knowledge to improve spinal cord repair and regeneration following injury.

Professor Martin Lowe

Professor of Cell Biology
Faculty of Biology, Medicine and Health
martin.p.lowe@manchester.ac.uk
Professor Lowe’s University Profile

GORAB & Geroderma osteodysplatica

The Lowe lab is investigating the rare genetic disorder Geroderma osteodysplatica (GO), which causes defects in the skin and bone similar to those seen in ageing; that is, loose, wrinkly skin and osteoporosis. GO arises from mutations in the protein GORAB, whose function is currently unknown. The lab is using classic cell biological approaches to determine the function of GORAB, and how its loss leads to the symptoms seen in GO patients.

Dr Chris Ward

Reader in Stem Cell Biology
Faculty of Biology, Medicine and Health
christopher.ward@manchester.ac.uk
Dr Ward’s University Profile

Differentiation of Neural Progenitor Cells from ES and iPS Cells

Dr Ward’s regenerative research focuses on the generation of neural precursor cells from both ES and iPS cells.  He also specialises in the isolation of iPS cells from Alzheimer’s disease patients to model tau aggregation. Other projects in his lab aim to exploit his research for commercial applications, including ES cell bioreactor culture and novel cadherin interacting peptides.

Developmental Biology

Professor John Aplin

Professor of Reproductive Biomedicine
Faculty of Biology, Medicine and Health
john.aplin@manchester.ac.uk
Professor Aplin’s University Profile

Embryo Implantation and Placental Development

The Aplin group investigates the molecular and cellular mechanisms of embryo implantation and placental development, as well as the implications for disease, treatment of infertility and disorders of pregnancy.   Their work bridges the clinical disciplines of reproductive medicine, obstetrics and maternal and fetal health. The group is embedded in the collaborative environment of the Maternal and Fetal Health Research Centre.  The Centre, with funding from Tommy’s:The Baby Charity, is using molecular, cellular, systems biology and integrative approaches for investigating aspects of pregnancy disease, including abnormalities in the way the placenta forms, grows, invades the uterine wall and develops a vascular system in early pregnancy to provide for the demands of the growing fetus.  Their research is founded on appreciation of the importance of the very earliest events in pregnancy for later health in the fetus, child and adult.

Cell Matrix Biology

Dr Qing-Jun Meng

Arthritis Research UK Senior Research Fellow
Faculty of Biology, Medicine and Health
qing-jun.meng@manchester.ac.uk
Dr Meng’s University Profile

Circadian Rhythms in Tissue Degeneration and Repair of the Musculoskeletal System

Circadian rhythms are the endogenous 24 hour cycles governing nearly all aspects of physiology and behaviour. In mammals (including humans), this rhythm is generated by the master clock (suprachiasmatic nucleus, SCN) in the brain, which entrains to the light/dark environment and co-ordinates the peripheral clocks in most major body organs and cells. Circadian clocks control ~10% of our transcriptome in a tissue-specific manner and disrupted circadian rhythms (e.g. during ageing) have been linked with various diseases, including metabolic syndrome, obesity, diabetes, osteoarthritis and increased tumorigenesis.
Research in this group focuses on the interface between ageing and circadian biology. We aim to 1) Identify the mechanisms underlying age-related changes in circadian rhythms in musculoskeletal tissues (cartilage, intervertebral disc, tendon and bone); 2) Establish the functional significance of various skeletal clocks in coordinating local physiology (tissue homeostasis and repair); 3) Explore the possibility of targeting body clocks in order to ameliorate disease progression and promote stem cell based tissue regeneration.

Dr Joe Swift

BBSRC David Phillips Fellow
Faculty of Biology, Medicine and Health
joe.swift@manchester.ac.uk
Dr Swift’s University Profile
Dr Swift’s Wellcome Trust Centre for Cell Matrix Research Profile

Mechano-Transduciton and Tissue Ageing

A cell’s behaviour depends on a combination of chemical and mechanical signals from the surrounding microenvironment. Stem cells, for example, can interpret matrix stiffness queues in deciding whether to differentiate or remain quiescent. Cells in mature tissue must also be appropriately regulated to meet the mechanical demands of their surroundings, with cells in active tissue requiring more robust cellular structures in the cytoskeleton and nucleus. How cells receive and decipher mechanical inputs, by feeling the compliance of their surroundings or by being subject to deformation, is a key area of research in the field of mechanobiology. The Swift laboratory is interested in how these physical inputs are transmitted from matrix to cell and how they are transduced into molecular signalling in the nucleus; they want to know how the cell then responds to these signals with feedback to regulate remodelling of intracellular and matrix structures. They are keen to understand how these pathways change during the ageing process, when our tissues stiffen and cellular capacity to repair and regenerate is diminished.

Dr Michael Sherratt

Lecturer in Molecular Biochemistry
Faculty of Biology, Medicine and Health
michael.j.sherratt@manchester.ac.uk
Dr Sherratt’s University Profile
BioAFM Facility

Tissue Structure and Mechanical Properties

The mechanical properties of tissues play a vital role in maintaining health. Elastic fibres, for example, allow tissues such the skin, lungs and blood vessels to deform and recoil whilst the giant protein titin plays a major role in elasticity of the heart. With ageing and disease these mechanical properties can change contributing significantly to patient morbidity and mortality. In order to understand these pathological processes and to successfully replicate the mechanical function of native tissues using tissue engineering strategies, it will be necessary to characterise tissue structure and mechanical behaviour. Dr Sherratt’s research aims to develop new methods to visualise and measure tissue structure and mechanical properties at nanometre (atomic force microscopy) and micrometre (microCT) length scales. Dr Sherratt is the academic lead for the University of Manchester’s BioAFM facility.