How neutrophil-microbiome interactions fuel inflammation in colorectal cancer, Research opportunities, Division of Health Sciences

A postgraduate research opportunity at the University of Otago.

Details

Close date: No date set
Academic background: Health Sciences
Host campus: Christchurch
Qualification: Honours
Department: Surgery (Christchurch)
Supervisor: Dr Annika Seddon, Dr Rachel Purcell

Overview

The microenvironment in colorectal cancer (CRC) contains a complex array of interacting molecular players including immune cells, oxidants, cytokines and the host microbiota. Certain subtypes of CRC are classified by extensive immune cell infiltration and this is thought to contribute to the progression of disease. Many studies have investigated the role of our most abundant white blood cell, the neutrophil, in CRC progression, and the neutrophil enzyme myeloperoxidase (MPO) has been explored as an inflammatory marker. However, further investigation into the drivers of neutrophil activation in CRC are still required.

During infection, neutrophils will respond to bacteria and/or their surface molecules such as lipopolysaccharide (LPS) by assembling the NADPH oxidase to produce superoxide. Superoxide is rapidly converted to hydrogen peroxide, which is then used by MPO to produce HOCl, better known as chlorine bleach. In some instances, the neutrophil will decondense its DNA and extrude neutrophil extracellular traps (NETs). These DNA-histone complexes are decorated with MPO and serve to trap and kill microbes. However, not all microbes induce NETs and the extent of neutrophil activation differs between species. NETs and MPO have been found within the CRC microenvironment and are generally associated with adverse outcomes. Strong oxidants produced by activated neutrophils can cause significant collateral damage to surrounding tissue, and further exacerbate inflammation.

This project will explore how neutrophils respond to exposure to LPS derived from three species of bacteria known to be abundant in immune infiltrated CRC. This research will provide new insight into how the microbes in our gut combine with immune cells to promote CRC. This may lead to new strategies for preventing or slowing the progression of this devastating disease.

This is one of a number of projects on offer for the 2023 intake of BBiomedSc(Hons) at the University of Otago, Christchurch campus.

Preferred student expertise

An interest in immunology, microbiology and cancer. Must be comfortable working with blood. Experience with aseptic technique an advantage but not required.