The role and molecular actions of Galectin-3 in peritoneal fibrosis formation

Description

Scarring is the abnormal healing process that leads to reduced functionality of a tissue, affecting health and wellbeing. We wish to understand the processes of scarring in the peritoneum at the molecular and cellular level which can ultimately lead to the development of novel and successful therapies.

The healthy peritoneum provides a gliding interface via its delicate mesothelial lining. If the peritoneum is damaged, fibrotic scars can develop which impair its function and can result in pain and adhesions which tether peritoneal tissues and organs together.

Galectin-3 (Gal3) is a protein with sugar-binding capacity, with functional roles in a range of fibrotic and inflammatory processes. It is highly expressed in immune cells, such as macrophages and T cells. Upon tissue damage, cytokines recruit macrophages to the site of injury within the tissue. Accumulation of Gal3 secreting macrophages at the tissue injury site promotes the immune cell activation process, and stimulates local myofibroblast formation and production of extracellular matrix proteins. This makes Gal3 an exciting potential regulator in fibrosis and scar formation in the peritoneum as its role in this process has not been studied yet. We hypothesise that Gal3 regulates the process of peritoneal fibrosis formation.

The aim of this multidisciplinary studentship is to determine the therapeutic potential of Gal3 in peritoneal scar formation.

We have established several experimental in vitro and in vivo systems which allow analysis of the behaviour of mesothelial and other peritoneal cells in response to external stimuli that can induce scar formation.  Furthermore, collaboration with an industrial partner will allow testing the efficacy and mechanisms of novel Galectin-3 therapeutics in these models.

You will be part of a vibrant research team at the Institute of Life Course and Medical Sciences (ILCAMS, University of Liverpool).

The project will address the following objectives:

I.          To elucidate the levels of Gal3 expression in macrophages and their presence and distribution in the normal, healthy human peritoneum, and in response to external injury stimuli using a human 3D in vitro peritoneal wall model;

II.        To determine the levels of Gal3 expression in macrophages and their presence and distribution in response to surgical scar induction in the peritoneum in mice compared to healthy mouse peritoneum;

III.      To explore the efficacy of novel Gal3 inhibitors using the in vitro and in vivo models.

The findings from these experiments will advance our understanding of the therapeutic value of Galectin-3 inhibitors in the response of mesothelial and other peritoneal cells to injury challenges. These outcomes could provide a path towards prevention of fibrosis and scar formation in the peritoneum.

This studentship will provide you with a highly sought-after skill set in attractive techniques including cell culture, tissue explant and 3D cultures, live cell imaging, multi-omics and data analysis. The project will also provide training in establishing in vivo skills including surgical techniques in mice, mouse genetics and lineage tracing.

As part of your training, you will integrate in vivo and ex vivo skills with high-end imaging -omics technologies and data analysis. Furthermore, you will obtain training with the company producing the Galectin-3 inhibitors.

The successful candidate will be based at the University of Liverpool supervised by Dr Bettina Wilm with co-supervisor Dr David Turner and Prof Lu-Gang Yu. Minimum requirements are an MSc or MRes in biological or biomedical or related sciences, and desired requirements include experience with large data set handling or in vivo skills.

We are interested in candidates wishing to advance their skill sets using in vitro/ex vivo and in vivo approaches, imaging techniques and data handling. Interested applicants are invited to contact Dr Wilm to discuss the project at: .

Applications will close when a suitable candidate is appointed. The deadline may therefore be subject to change. 

Applications should be made to project supervisors in the first instance via CV and cover letter. This is for all applications. Only when a candidate has been selected following interview will a formal online application be required.