During last week’s WCMR ‘Research in Progress’ meeting, we heard from 2nd year PhD student Gareth Ettridge. The title of his talk was “Screening a Screen: Searching for the Haystack that has the Needle” but what exactly does this mean? Here, Gareth explains more.

Trying to find a new treatment for mitochondrial disease by screening many millions of possible candidates can be like finding a needle in a haystack. But when working with natural compounds, just finding the one haystack in the world that has the needle is a challenge in its own right.

It is well known that some natural compounds can influence mitochondria and bring about changes in how they function. This can include inducing mitochondrial proliferation, or the production of new mitochondria, which could be of potential benefit to those affected by mitochondrial diseases. To investigate this further, the WCMR team have set up high throughput screens to look for mitochondrial proliferation in cells treated with samples containing a mix of natural compounds prepared by an industrial partner.

During my PhD project, I have conducted experiments with these samples using a number of different techniques. The experiments have mainly focused on growing cells in the presence of each sample, and then using fluorescence microscopy to measure the amount of mitochondria within the cells. An increase in the total amount of mitochondria can be seen as an increase in fluorescence,  indicating that mitochondrial proliferation has taken place.

There is one major issue when working with natural products. All samples are impure. The active compounds that are actually having the potentially beneficial effects are unknown, and they are hiding within incredibly complex mixtures (the rest of the sample). A lot more work is required to identify these active compounds and work out exactly what they are doing.

In summary, it is likely that this project has found a handful of sample ‘haystacks’ in the world that could be interesting, each of which could have its own active compound, or ‘needle’. The next tasks are to find the active compounds, work out how they are having their effects, and then see whether they could be of use as a future potential treatment for mitochondrial disease.