Ear-microbiome

This project is a pilot study on severe ear disease (otitis media, OM) in children that uses a new technique to study both the body's response to OM and the activity of bacteria in the middle ear. The study aims to: 1) Identify what the human cells in the middle ear of children with otitis media are doing in response to the disease. Specifically, we want to know whether low oxygen concentrations in the fluid-filled middle ear are prompting a response from the cells that causes inflammation, as this could reveal a new way to treat OM. 2) Determine which species of bacteria are active in the middle ear of children with OM, and to look at what they are doing in this environment that may contribute to the disease. 3) Apply a new method called dual RNA-seq to middle ear fluid samples for the first time, to measure the human and bacterial molecular activity together within the same sample
Person

Principal investigator

Sarra Jamieson rachael.lappan@research.uwa.edu.au
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Area of science

Biology, Medical And Health Sciences, Microbiology
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Systems used

Nimbus
Computer

Applications used

FastQC, Trimmomatic, Bowtie2, SortMeRNA, HISAT2, StringTie, SAMSA2
Partner Institution: Telethon Kids Institute | Project Code: ear-microbiome

The Challenge

Otitis media is the medical term used to describe a related group of conditions affecting the middle ear that are all characterised by inflammation and fluid behind the ear drum. This group of conditions includes middle ear infections, associated with pain and fever with pus from active infection seen behind the ear drum, and glue ear, where a sticky fluid builds-up in the middle ear leading to reduced hearing levels. These conditions are both common in childhood and most children will be diagnosed with an ear infection or glue ear before they reach school age. However, some children suffer repeated ear infections or persistent glue ear in their early years. These children are often referred to an Ear, Nose and Throat (ENT) specialist who may recommend a surgical procedure to insert a small ventilation tube (or grommet) into the ear drum. This grommet allows any pus or sticky fluid present in the middle ear to drain away and restores hearing to normal levels.

We currently don’t fully understand why some children suffer repeated ear infections or persistent glue ear. Research shows a number of risk factors play a role, including exposure to certain bacteria and viruses and whether a child has allergies. There are also several environmental factors that can influence whether a child gets otitis media, for example whether they have brothers or sisters or whether they attend daycare. It is also not clear what the clinical relationship between ear infections and glue ear is. It is known that glue ear can follow on from an ear infection; however glue ear can also occur on its own without an earlier ear infection. By understanding the body’s response to ear infections and to glue ear we hope to provide new insight into how these conditions may relate to each other as well as potentially help to identify novel treatments and interventions for these conditions

 

The Solution

The research undertaken by our group is aimed at understanding why some children suffer repeated ear infections or persistent glue ear. In this study we will look at how the body responds to ear infections and to glue ear. The way our body responds to its environment (including its response to an infection) is determined by our genes. Genes are switched on or off as needed and we can accurately identify which genes are switched on (are expressed) at a particular time by measuring the levels (quantity) of the message (or gene transcript) produced by each gene. To do this we will use a relatively new technique called dual RNA-Seq. This technique allows us to identify all of the genes that are being expressed and the quantity at which they are expressed in a sample. This technique has the capacity to not only look at which of our genes are switched on but also which bacterial genes are switched on. This information can then be used to identify bacteria that may be present, and what they are actively doing in the middle ear that may contribute to ear disease. This will allow us to better understand the processes that lead to repeated ear infections or persistent glue ear, which can help us identify new ways to prevent or treat them.

The Outcome

The computational resources of the Pawsey Centre allow us to process the large volume of RNA sequencing data generated by the project. Millions of biological sequences are analysed at once to identify their function, which cannot be achieved on a standard personal computer.

List of Publications

Profiling the microbial metatranscriptome and host transcriptome of middle ear fluid using dual RNA-seq (Thesis chapter). This thesis (Using ’omics technologies to understand pathogenesis and seek alternative therapies for otitis media in children – Rachael Lappan) is currently under examination.