Inside the lab with Issie
Hi Issie, can you start by telling us what your research is all about?
The Trust funds a Strategic Research Centre (SRC) of which I am a part of. This collaboration is directed towards finding treatments for people with CF who are currently unable or are unsuitable for modulator therapies.
My project focuses on investigating which type of lung cell to edit, whether the gene editing has restored function of the CF protein within airway cells, and what proportion of cells need to be corrected to restore lung function to normal.
What’s a typical day like for you?
Working in the lab is flexible from day-to-day, so no one day is the same. Usually, I’ll have a plan for the week for specific experiments. It can mean some very early starts, or at other times I’ll finish late in the evening. I also have time to sit at my desk and read about the work of scientists working in similar areas of research.
Talk us through a gene editing experiment, step by step!
Step 1: Preparing gene editing materials. The first step is to prepare the materials that actually edit the DNA, and biological markers to track the progress of the experiment. It takes a week to generate enough material to do the experiment. The materials are packaged into a ‘vector’ – the best way to describe this is a biological envelope – to get the materials into cells.
Step 2: Growing lung cells in the lab. At the same time as step 1, I grow lung cells in special dishes in the lab, where the bottom of the cells are in liquid and the top of the cells are open to the air. This is known as ‘air liquid interface culture’ – or ‘ALI culture’ for short. I grow the cells this way as it mimics the environment on the surface of the lungs.
Step 3: Allowing gene editing to take place. When it’s ready, my gene editing mixture is then added as a liquid onto the airway surface of the lung cells and incubated in a warm, gassed incubator. The next day, as if by magic, gene editing may or may not have occurred!
Step 4: Checking whether the gene editing has worked!
Step 4a: Have the materials arrived? Within the gene editing materials are the instructions to make a fluorescent protein. If the lung cells read these instructions, the cells fluoresce under a microscope! This means the materials have made it into the lung cells. Usually some cells fluoresce and some don’t – it’s the first part of testing whether the gene editing has worked. We also check for changes in the lung cell DNA too.
Step 4b: Has the editing improved the function of the CF protein? If we see that editing has occurred, we can then move on to test the activity of the CF protein, to see if it is actually working. We do this in two ways, either by measuring tiny electrical currents across the cells, or by measuring the acid-alkali balance of the liquid above the surface of the cells.
Here’s an explanation of how these two different tests work:
Measuring tiny currents: When I measure the electrical currents, I’m measuring the flow of ions (eg chloride or bicarbonate) through the CF protein channel. (There are lots of other channels opening and closing at the same time. I know it’s the CF protein channel by adding medicines that increase or decrease the CF channel activity).
Checking the surface liquid: The liquid that lines the surface of the lungs needs to be kept at the right acid/alkali balance (the right pH balance). In CF the liquid becomes too acidic, this is because an alkaline chemical called bicarbonate is missing. Bicarbonate is transported through the CF protein channel. When the CF protein is working, bicarbonate can move to the surface and the acid-alkali balance is restored.
What do you love most about working in research?
Working in research is exciting. Being able to ask a question and then plan how best to answer it by producing data to support this is extremely fulfilling. I also appreciate the ability to structure my day around each project and being able to work independently as well as help others in the lab.
How do you relax at the end of the day?
My favourite thing to do outside of work is to spend time with my partner and cat. When we have time, we try to play tennis or badminton, and we are big fans of TopGolf.

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