We ask what are the most challenging and rewarding aspects of their careers so far, where we're at with gender equality, and what they'd share with those coming up the single-cell ladder.
Single-cell genomics is an exciting, emerging bioscience field that can make a real-life impact to human and environmental health. We speak to the predominantly female EI team about how they found themselves in the sector and what they’re currently working on; confronting biological questions by developing cutting-edge methods and techniques.
N.B. This is the first instalment of a two-part feature series entitled Women in Science: Single Cell Genomics. Read the second half of this feature, here.
I always liked biology. To be honest, biology as an undergrad was only my second choice, but I’m so happy with my decision. As a PhD student, I was working in the field of molecular biology and systems biology, and I first met the EI single-cell genomics group when I needed fluorescence-based cell sorting for one of my experiments. I think one of the most important things single-cell genomics points out is how different each individual cell in a population can be. Because of that we can get a much finer picture about their function and communication if we look at them separately. Also, single cell or low input experiments make it possible to look at rare cell populations, which would have been impossible in the past.
In the last couple of years I had both computational and wet lab projects, such as learning to use the R programming language to handle and analyse large datasets; comparing protein-protein interaction predictions and analysing networks of interactions using Cytoscape to gain insights into bacterial effects (e.g. Salmonella) on human cell processes on a systems level. On the other hand, I was working with bacterial and human cell cultures in the lab, analysing the gene expression changes upon bacterial infection. Experiencing these two sides is an interesting mix, but also challenging as it requires quite different skillsets - it is especially exciting to aim to validate my own computational predictions in the lab.
Since joining the Macaulay Group, I’m learning to do bisulfite sequencing and analysing methylation data, which we would like to use in different projects, on low input or single cell samples. The first project aims to analyse the effect of Bifidobacteria on different epithelial cell populations in the ileal crypts (birthplace of all cells that line the gut) from mice - a key project in EI’s Core Strategic Programme in collaboration with the Korcsmáros Group.
Definitely what’s most challenging in my career is dealing with uncertainty in science. There are usually no clear, definite answers to our questions, and this is hard sometimes. The most rewarding is when the pieces of a project click together, and it becomes a whole. I’d advise starting to get involved in many projects and techniques as soon as possible. It may take time to find the place - group, topic, Institute - where you feel like it’s the right one for you, so sooner and more experience you get the better.
I don’t think the fact that we’re a mostly female team has anything to do with gender equality, otherwise it would suggest that it is biased towards women. I personally never felt that there were fewer or more opportunities for me because of being a woman.
I’ve always been interested in science from a very young age. My mum owned her own manipulating pharmacy in Brazil, where I loved to be with her in the lab and watch her preparing cosmetics and capsules for her customers. That’s probably where my love for the lab and aspiration towards science first began. At university, I studied Molecular Biology and Genetics, followed by a master’s in Molecular Medicine. Single-cell genomics is something I got into when I started my PhD at EI; it wasn’t part of the teaching material at university as the field was and still is relatively new.
My project revolves around studying the differentiation patterns of haematopoietic stem cells, a rare population of cells within the bone-marrow responsible for giving rise to all the cells found in our blood. My goal is to understand how a subpopulation of these stem cells, once thought to exist as a homogenous population of cells, can be biased towards megakaryopoiesis – the pathway responsible for producing platelets.
Understanding cell differentiation patterns by studying gene expression and how genes are regulated at single-cell resolution enables us to better understand complex tissues composed of many different cell types and states. Developing techniques to obtain as much information from the same single cells is revolutionising fields such as haematology and cancer biology, and many more.
My ideal research project would ask a biological question which requires a good level of defiance while at the same time yielding results with impact that would progress the field - surrounded by not only inspiring scientists, but good and friendly people willing to provide support both in the project itself and as colleagues. I am very fortunate to be able to say that I have the ideal [research project] in my eyes, and I am excited to come into work every day!
Definitely the most rewarding has been to present and discuss my work with fellow scientists, both from and outside the single-cell field. To see enthusiasm from others regarding my work always fills me with a great sense of pride and shows me how much I have learnt in my project so far. I guess the most challenging is to keep up with the continuous flow of papers being published introducing new methods or pipelines to analyse single-cell data. It can get overwhelming!
I am very fortunate to be able to say that I have the ideal [research project] in my eyes, and I am excited to come into work every day!
Being part of a female team is great and is hugely encouraging for my future career in science. From that side gender equality in science seems better. However, you still see far fewer women progress to more senior roles in science, for instance, seeing fewer women principal investigators than men. I am not discouraged by it, but it is definitely something I am aware of and have to keep in mind as I develop my career.
I’m still exploring ideas of different opportunities after completing my PhD. I know I’ll continue to pursue scientific research, but I hope to gain a better understanding of this both in academia and Industry during my project so that I can get a postdoctoral research position in a field that best suits my skills as a scientist.
My advice for anyone getting into single-cell genomics is to try as best you can to understand the range of single-cell protocols and technologies, and how they are being used to answer different biological questions. Each technology has its advantages and disadvantages and understanding which approach would best be applied to tackle your research question will not only save you time (and money!), but will be the most likely way to generate the results you need to progress.
As a Research Assistant, sometimes the ‘career’ moves I followed were based on the skillset I had acquired and upcoming grants; saying that, every new job has been more exciting. My position in the Macaulay lab is the best so far and suits my interests; the way that I like to work and surrounded by influential and supportive people.
Previously, I had been in various molecular genomics roles, leading to working with the Genomics Pipelines Group at EI where I learned everything there was to know about automation, library construction and sequencing. With this extra knowledge, and the skills I had from previous roles (cell culture, microscopy cDNA synthesis and RNA and DNA extractions) I could use this experience to apply for my current role.
In my assistant role, sometimes I feel like I don’t have a specific project as we have a huge amount of collaborations in part due to our BBSRC Capability status, but also because of our core location here at Norwich Research Park. I have worked on diverse projects sequencing diatoms, protists, zebrafish sperm cells, cow immune cells, human immune cells, mouse blood cells, cancerous cells, chick embryonic cells, as well as arabidopsis plant protoplasts made from tapetal cells and leaf tissue.
My current project is studying a cell type called meiocytes, which are cells going through meiosis, in wheat. I would like to understand the mechanisms that control meiosis (a type of cell division responsible for the development of sexual cells required for breeding such as the sperm and oocytes). By understanding more about the mechanisms behind breeding, we can use this to aid the introduction of useful traits such as pathogen resistance, environmental tolerances or increased yield.
As it’s not common practice, I would like to see single-cell genomics applied to plant cell biology to increase our understanding of plant biological systems including breeding, pathogen resistance and nutrient uptake. It will also be of importance in the generation of genetically-modified crops and the understanding and efficiency of the current process. Another big impact is looking at the composition of the microbiome of healthy, immunocompromised, antibiotic-treated, or ill patients and how this affects their future health. There are a few scientific groups that are looking at microbiome replacement therapies, and this is really promising.
I have an idea that would greatly increase the rate of plant breeding using some of the protocols I am currently developing but including extra steps. There are impossibilities in a couple of stages currently, so even years on if I could get this whole, dream protocol to work, it would be incredibly useful in feeding the world’s ever increasing population.
The most challenging [aspect] is balancing my workload with being a new mum.
Ashleigh Lister (right), Research Assistant, Macaulay Group at EI (Group leader Dr Iain Macaulay, left)
I am incredibly proud of journal articles as a named author, and how each new role I've achieved feels like it’s a reward for the skills I’ve worked really hard to learn and get right. The most challenging [aspect] is balancing my workload with being a new mum. I have dropped my hours to four days a week and some weeks I feel that I’m attempting to run between simultaneous tasks. This is made a hundred times harder when I must drop everything to collect my son from nursery when he is ill.
Our mainly female group is very fortunate with being selected as the best candidates for our roles. I wouldn’t say that gender equality is necessarily improving in science; if it is, it’s not that fast. For those considering starting a family, there is a long-standing question of when to have a child in a woman’s career, and this is not improved by short-term contracts based on grant-funded work and heavy competition to produce articles in high-impact journals. Often, it is difficult for a wet-lab scientist to conduct long protocols in short days, or part-time hours, forcing them into more office-based roles, possibly out of the science sector all together.
As a career ambition, I’d like to turn the journals I have, and would like to be part of soon, into a PhD by Publication. This is a really exciting prospect, even if it’s just to plan my own experiments! I will be trying to learn some data analysis to be able to understand the data I’m producing independently. Although, starting with single-cell wheat is jumping in at the (very) deep end!
What I'd suggest for getting into my field is to make sure that you get sequencing experience, the whole process; from sample preparation, library construction to loading a sequencer. It is so important to know how your data is formed. If you can, and I haven’t mastered this yet, learn some bioinformatics - a good place to start is with ‘R’.
N.B. This is the first instalment of a two-part feature series entitled Women in Science: Single Cell Genomics. Read the second half of this feature, here.
