Profile

I live with my partner, Liam, in York. We are both into video games, TV and films. I also play the piano and enjoy listening to music. I have recently taken up running, but I am still not very good at it.

Muscles grow when you use them, and shrink when you don’t. This happens because muscles can ‘listen’ to certain signals which tell it when you are using them. When these signals go wrong, or your muscles can’t listen to them properly, this can cause muscle diseases.

There are different types of signal that your muscles can listen to: –

Nervous system signals: I’m currently typing because my brain is sending electrical signals through my nerves into my hand muscles. Muscles can sense that these signals are active. If my nerves were damaged in an accident, these signals would stop and my muscles would start shrinking (the fancy term is denervation-induced atrophy).
Energy signals: Using your muscles a lot uses up a lot of energy. Muscles can sense the amount of energy being used and make more mitochondria – the energy factories of a cell – to help your muscles keep up.
Growth factor signals: Growth factors are molecules which help make things grow. If you have lots of these floating around, this will help muscles to grow. There will be more growth factors around if you are eating well. If you don’t eat enough, this will lower the levels of growth factors. If things get particularly bad, your muscles will start eating themselves to produce energy (fancy term: autophagy)
Stretching signals: Some molecules in your muscles will stretch and contract as you move your muscles. This can cause that molecule to change shape temporarily. This may cause other molecules to be released or altered, which can be detected by your muscles.
Damage signals: If you exercise a lot or try and lift very heavy things, some of the molecules in your muscles will break. This sounds like bad news, but it actually turns out that this damage helps to tell your muscle that it should grow to become stronger. Of course, if you have too much damage this causes an injury, so be careful!

My PhD project is looking a bit more at this last type of signal. We are trying to figure out if a particular molecule, called KY, helps muscles to detect and deal with muscle damage. Mutant mice that don’t have KY have a disease where muscle damage seems to build up over time, and their muscles are smaller and weaker. So I’m trying to figure out what KY does and why it is important.

One way I am doing this is by making mutant muscle cells and mutant zebrafish. By seeing what happens to these when we stop them from making KY we can get more clues about what KY does.

The way I make mutants is using a relatively new technology, which is called CRISPR/Cas9. Essentially, you can design a molecule that will hunt down the gene you want to mutate and attract an enzyme to your gene which will break the DNA. This stops the gene from working properly. Below is an example of a test experiment I did with zebrafish. I targeted the gene that is responsible for making the dark spots (pigment). The top picture is a normal fish embryo, and the bottom picture is a fish embryo where the gene has been completely broken. In between are fish embryos where the gene was broken in some parts of the fish, but not others.

What I do each day can change quite a bit depending on whether an experiment is working well or not, but most of my working day is spent in the lab. The things I spend the most time doing are: –

Playing around with cells – you can grow muscle cells in the lab and see what happens when you stretch them or treat them with different chemicals. I’m trying to figure out if cells without the KY molecule respond any differently to normal cells.
Taking care of my zebrafish – animals that are used in research are all treated very well and part of my job is to look after the zebrafish to keep them well fed and healthy. I have made some mutant fish which don’t make the KY molecule, but it is too early to tell if anything interesting is happening.

A pair of camera shy zebrafish