Researching to beat antimicrobial resistance: A day in the life of a CF research student

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This week it is World Antimicrobial Resistance Awareness Week (WAAW). Antimicrobial resistance (AMR) is where medicines such as antibiotics or antifungals are no longer effective at treating infections, as the bugs have developed ways to avoid their effects. PhD student Elliot Mahoney is investigating new ways to treat complications arising from Aspergillus fumigatus infections in people with CF, a fungus that is becoming resistant to current antifungal treatments. To find out what this means on a day to day basis, he talked us through a typical day in the lab.

The aim of my research is to understand how a type of immune cell called neutrophils respond to Aspergillus fumigatus infection. Our immune system is a very complex network of cells and chemical signals that make up the body’s self-defence system.

Neutrophils are immune cells found within the blood. They’re one of the ‘first responders’ when we develop infections. However, when people with CF develop lung infections, the response of neutrophils is excessive, which can make the infection worse. We want to know if we can use immunotherapy medicines to turn down this response as a way of treating Aspergillus related complications such as Allergic Bronchopulmonary Aspergillosis (ABPA). But to do this we need to understand in much more detail how the neutrophils in the lungs of people with CF are responding to Aspergillus infection.

My typical day

It can take weeks of prep work to get ready to do some experiments, getting different bits ready separately. It means that on a typical day I can be working on several different stages at once. On the Monday these photographs were taken, I was extracting neutrophils from a donated blood sample and keeping human airway cells growing in dishes.

This particular blood sample was kindly donated from someone who doesn’t have CF. We always need to compare what’s happening in samples from people with CF with samples from people who don’t, so we can understand any differences due to CF.

Photo of Elliot working in the lab

Photo 1: We decant the blood from the collection tubes and then layer it over a dense liquid ‘medium’. It’s almost like adding the cream (blood) on to a liquor coffee (the dense medium)! The medium has special properties which will separate out all the components of the blood.

Photo of lab centrifuge

Photo 2: The samples are spun at 616 g for 20 minutes in a centrifuge. (‘g’ is an abbreviation for ‘g-force’. It is the same thing that people talk about when talking about rollercoasters, or Formula 1 drivers. The samples are exposed to ever 100 times more g-force than a Formula 1 driver experiences going round a corner on a track! But this is a gentle spin in terms of lab centrifuges!).

Photo of tube of separated liquid in the lab

Photo 3: After the spin, the blood has separated into different layers. The top, yellow part is the plasma, the dense medium is next, and red blood cells and neutrophils are in the bottom layer.

A photo of a pellet of neutrophils in a lab tube

Photo 4:  A final step is needed to get rid of the red blood cells. This is done by adding a solution to break open the red blood cells (kill them), which makes it easier to separate the neutrophils. The neutrophils are the white pellet at the bottom of the tube.

These neutrophils were used to look at a specific reaction they have during an Aspergillus fumigatus infection.

Keeping airway cells growing in the lab

We study what might be happening in the airways of people with CF during Aspergillus fumigatus infection using a common lab technique, where we grow human airway cells in little dishes called culture plates.

On this day, I’m mid-way through growing some airway cells for these experiments. The airway cells are grown for two weeks. This is so that they can get used to their new environment and form interactions between each other, like the cells in the airways would have naturally, before our experiments start.

Photo of cell culture scaffold in the lab

Photo 5: In my hand is a scaffold, the base of which is like a sponge with tiny holes in it. The airway cells are grown on this sponge and form 3D layers. The sponge sits in the dish, where the bottom surface of the sponge (and so the bottom of the airway cells) is in liquid, and the top half is in the air, mimicking what it is really like in the airways.

Photo of research maintaining cell cultures in the lab

Photo 6: The cells need to be fed every couple of days (including weekends!) to keep them healthy and happy. All of the liquid, containing the waste the cells produce, is removed, and fresh liquid with more food is added.

Photo of cell culture incubator in the lab

Picture 7: After they’ve been fed and changed, the cells are placed back into their incubators. These keep the cells happy at 37°C and 5% CO2, which mimics the inside of the human body.

After two weeks the human airway cells are ready to be infected with Aspergillus fumigatus, the neutrophils are added and our experiments can begin.

What I love most about my job

I love what I do because each time I go to work and put on my lab coat, I feel the same giddiness I used to get doing experiments at school. I like the satisfaction of when you get the results you expected, or the excitement when the results show something new and unexpected.

At the end of the day there’s the knowledge, or hope, that what I’ve done will one day help people with CF.


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