Image credit: Wellcome Sanger Institute
Dr Ore Francis is a Postdoctoral Fellow at the Wellcome Sanger Institute. One of three inaugural Excellence Fellows, Ore is exploring the proteins that are at the root of all life on Earth, answering questions about adaptation and evolution along the way.
Starting at the beginning, how did you become interested in science?
I have always been curious about how things work, but I only chose to study biochemistry at university because I liked the sound of it. At university, I realised I enjoyed benchwork and I accepted a role as technician shortly after. For me, it was the hands-on experience that fostered my interest in science.
A lot of my work since then has involved proteins, which are crucial building blocks of life. I also study protein complexes, bound groups of two or more proteins that have fundamental roles in all life forms. My PhD was spent exploring the functions of proteins (in my favourite protein complex) and how they vary across species.
The Muskelin/RanBP9/CTLH complex was thought to be involved in cancer in humans, and I found equivalent proteins that make this complex were present in thousands of other organisms, many without additional expected proteins that are involved in cancer. It sparked my curiosity and I wanted to explore more about how protein complexes of different organisms are related, and how they have evolved.
It was also the first time I had been aware of the diversity of the eukaryotes outside of the animals, fungi and land plants — the protists. This might have been a later stage to develop an interest than for a lot of scientists, but I think it’s important for showing that scientific interests developed later can still contribute to great projects.
We hear a lot about the complexity of life but I’m really interested in where these systems have come from. I think there is still so much to be uncovered and so many puzzles to solve within this area, which keeps me engaged and pushing forward in my research.
Can tell you us more about what you do at Sanger?
I am working in the Tree of Life Programme, where I am looking for genes that correspond to protein complexes in eukaryote genomes.
I’ll be doing this by adding more protist genomes then searching the genomes of organisms (including protists, animals, fungi and plants) to find genes that are equivalent to genes already known to code for proteins of complexes in other organisms (orthologs). I’ll also look at different parts of these proteins and use machine learning to identify other proteins that likely form complexes in organisms yet to be studied. Ultimately, I hope to summarise my findings in a database for other researchers to use.
Genomes hold the genes that are instructions that the cell uses to create proteins. Protein sequences and complexes have similarities across species, and you can see in the evolutionary path how some of them are connected.
Protists are (mostly) single-cell eukaryotes. They are considered ‘higher’ life-forms like us, plants and fungi, compared to non-eukaryotes such as bacteria. Although there is far less variation in size, compared to animals, plants and fungi, the majority of eukaryote genome sequence diversity is within this group. To compare protein sequences across eukaryotes, protist genomes are necessary as well as animal, fungi, and plant genomes.
However, the scientific community is selective over which organisms are targeted for genomes, guided largely by economic relevance and disease. Protist genomes in particular are underrepresented relative to other eukaryote genomes. As part of the Darwin Tree of Life project, we will add more protist genomes, but we will probably add protist genomes from outside of the UK too.
By filling in gaps in our understanding of protein complexes in protists, I am working on predicting which proteins were in the complexes in the ancestor of all eukaryotes.
What’s the most surprising thing you’ve learnt?
The most surprising thing I’ve learnt is how much we haven’t quantified. It is rational to assume that the ~1.5 million named species are the summation of human taxonomic study to date and to get a sense of completion about it. But the truth is there are so many more species estimated to exist.
What is your favourite thing about research?
My favourite thing about research has probably been talked about elsewhere as flow or momentum. A lot of the planning behind experiments can be fiddly and stressful, but when everything is in place to complete an experiment or even to write about it, I often feel like I’ve had a good time.
Another of my favourite aspects is the discussions that take place. Sanger is the perfect place to be when it comes to collaboration and talking to people in different fields.
It’s great to be able to get other experts’ thoughts on data or sequence analysis, and I really like the way that researchers are happy to help figure out the language to communicate complexity in different ways or find new ways to apply data.
What barriers have you had to overcome in your work?
I think the biggest barriers in my career are self-imposed, from where I have changed disciplines multiple times. However, I wouldn’t change this as I’ve always followed my curiosity and I’ve always enjoyed my work. I went from biochemistry to microbiology to immunology and then to bioinformatics at Sanger, which is the first time I will be working with genome sequencing. While this means I have to learn new things with every move, I wouldn’t ever discourage anyone from changing disciplines and following their interests as it gives you skills and passions that you otherwise might not have known about.
Tell us something about you. If you could travel anywhere, where would you go?
The difficulty here is choosing just one place! I want to visit a whole host of places including Madagascar, Brazil, Ghana, Sweden and I would love to drive along Route 66 in America. In general, I like to meet and learn about people who are different to myself, both in work, locally, and further around the world. Travelling and exploring new places would be a great way to do this, while seeing some amazing views at the same time.