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 second instalment of this series, you may wish to read part one of this Women in Science: Single Cell Genomics feature first.
During my PhD, I was intrigued by the clonal diversity and dynamics in the blood system. Blood stem cells by phenotype look very similar but can have completely diverse functional characteristics. Therefore, single-cell molecular and functional assays are instrumental to dissect this heterogeneity. Single-cell genomics allows us to study the evolution of cell clones including malignant clones. This information can facilitate the development of personalised, targeted therapies to revert cancer from lethal to chronic disease type.
Currently, I am studying how blood stem cells produce all mature blood cell types, by applying single molecular and cellular barcoding methods to understand what the key regulators of the differentiation process are. This knowledge will help recapitulate this process entirely in the petri dish in the laboratory with the efficiency comparable to that in our body. I’d like my project to validate if the method I’m developing can provide us with a deeper insight into the differentiation process. If so, one day I would like to focus more on the translational aspect of my findings.
One of the most important, and at the same time challenging, tasks in science is to find a burning question and secondly how to tackle it. The most rewarding part is to find the answer to this important question, which in future can have translational implications. Thanks to the Sir Henry Wellcome Postdoctoral fellowship, I have a great opportunity to work on my own project on blood cell development. State-of-the-art platforms including liquid handling robotics, automation, sequencers and expertise in molecular biology and bioinformatics available at EI provide an excellent and unique environment to leap into this challenging and fascinating project.
For those wanting to get into single-cell genomics, I recommend performing experiments for the first time; diving into the unknown and understanding biological circuits is fascinating. In science, you must be persistent and at the same time discuss with your colleagues, exchange ideas and collaborate to bring the required expertise to confront ambitious yet relevant biological questions.
Single-cell genomics can provide very detailed information and enable us to look at tissues at an unprecedented resolution. We are able to define which types of cells compose a tissue and how they work together to develop and conserve the tissue during an organism’s life.
Moreover, we can describe what changes happen when a disease initiates and progresses - and in which most sub-groups of cells within the tissue, these changes occur - whereas this information remains hidden when performing a bulk study. This kind of analysis can be applied to every tissue and organism; to study meiosis; how a tissue develop during embryogenesis; or which group of cells in a tumour develop resistance.
My project at EI aims to develop novel single-cell sequencing approaches that provide more information about how transcription, the process to translate DNA into RNA, is regulated and apply the approach to study blood stem cells. In particular, to define if blood stem cells are heterogeneous and primed to differentiate into a specific type of blood cells, and how the stem cell makes the decision to start differentiating. As blood stem cells seem to lose their ability to properly replenish blood tissue when the organism ages, we are applying this approach I developed to studies where cell changes may cause this loss of function.
I have been fascinated by biology, in particular genetics, since I first studied it at high school. I decided to study biology at University; during that time and throughout my PhD I became really passionate about molecular biology and research. I got into single-cell genomics gradually, moving into genomics first during my postdoc, when I had the opportunity to learn about all the different technologies and their potential to study disease. I was really fascinated by the idea of looking into a tissue cell-by-cell and finding out how they maintain the tissue, and what happens when disease occurs.
In my science career, one of the biggest challenges is to learn to deal with failure. Science requires time and dedication and sometimes you may not get the results or the output you expected. It can also be quite difficult to balance a personal life with non-permanent jobs and the need to move to a different lab and city, or sometimes country. It is really rewarding, on the other hand, contributing to advancing scientific knowledge and hopefully making an impact. My ideal research project would be one in which I could develop a novel technology and use it to answer a crucial biological question.
I feel gender equality is becoming better, however, I think there is still a gap in more senior positions. In the future, I would like to keep working in research to gain more knowledge and scientific independence - the best thing you can do is to be really passionate about your science and don’t be afraid to ask your peers for help and suggestions.
One of the biggest challenges is to learn to deal with failure. Science requires time and dedication and sometimes you may not get the results or the output you expected.
~ Laura Mincarelli, Postdoctoral Scientist, Macaulay Group at EI
As part of my PhD project, I will be using single cell multi-omics techniques in patient-derived organoids of colorectal (bowel) cancer. These cells will be exposed to a particular treatment and we’ll aim to identify the differences between treated and untreated cells to understand cancer evolution and drug resistance at the single cell level. In the future, I would like to understand the intra and inter-tumoral differences between breast cancer patients with the same cancer type; and work not only with cell lines or organoids but also with co-cultures, patient-derived xenografts and clinical samples.
I’ve always been interested in cancer, so I studied Biomedical Science at undergraduate and postgraduate level to have a deeper understanding of the subject. I worked for a while in Histopathology, which essentially looks at the expression of target proteins in human and animal tissues and how these relate to the progression and treatment of cancer.
However, I wanted to understand cancer at the genetic level and how, even though two people could have the same cancer type, they may respond differently to the same treatment. I started to look at PhD projects and came across the beneficial idea of sequencing DNA/RNA from single cells instead of bulk tumours.
Single-cell genomics has the potential to identify intra-tumoral differences between same-cancer patients. I believe that, in conjunction with other techniques, single cell analyses could be eventually translated to the clinic – once the costs are lowered – with the aim of characterising every single aspect of a disease to find the most effective approach to target specific patients.
Cancer is like a jigsaw puzzle composed of many pieces. When you buy a puzzle, the pieces are all scattered inside the box and you are only given a picture to assemble the puzzle. With cancer we have the opposite, we must make sense of a pre-assembled puzzle. This is because we can only identify cancer when it’s already there; big and harmful. It’s easy to understand or see what the puzzle represents once it’s been assembled, but harder when the pieces are all muddled up.
We already have plenty of information about bulk cancer tumours, enough to conclude there are intra-tumoral events that can’t be understood solely by looking at the whole tumour, but instead, at every single-cell type that makes the tumour behave in a particular way. Currently, there are many treatments for cancer that work - but we still need to understand cancer better so that it doesn’t come back, and if it does, be ready to fight back. For this, it is crucial to know how it arises, changes, evolves and adapts – which can only be attained at the single cell level. Eventually, it would be fantastic to characterise all cells so deeply that you could take any cell from any state and identify specific genes that will drive its fate and ultimate behaviour.
In my work, I’ve found the most difficult thing is to read scientific papers in a language different to mine. Also, it was hard to commit to one scientific field to study cancer. I would love to have a thorough understanding of cancer in terms of histology, genomics, bioinformatics and proteomics. There are always new techniques to learn but not everyone has access to them. I find it most rewarding to work in something I’m very interested in. Hopefully, the techniques I’ll be working on throughout my PhD will one day be used to improve people’s health.
We still need to understand cancer better so that it doesn’t come back, and if it does, be ready to fight back.
~ Silvia Ogbeide, PhD student, Macaulay Group at EI
In terms of gender inequality in science, I wasn’t aware there was any. However, as I’m encountering older female scientists, I’m starting to realise that for a woman, the main challenge is being able to balance your professional and personal lives when there are children involved.
My career aim is to work in Translational Science and do research that could potentially help people who may need it. For others coming into this area, think of something you are interested in. Could single-cell genomics be used to understanding this better? If the answer is yes, then find a way to get into the field.
