Curiosity about the world around has long been a symptom of the human condition, whether looking outwards at the stars or the oceans, or inwards to discover what makes us who we are. One of the things that drew me to science is its focus on asking questions about our world, and designing tests to practically investigate things we don’t know.
In 2007 I had just started my undergraduate degree, picking a broad life sciences course to give myself room to decide what would best spark my curiosity. At around the same time, new studies in humans and mice were discovering that cell fate (being restricted to a final cell identity) was more flexible than we might have imagined. Specialised cells that are otherwise committed to their identity, like skin cells, could sometimes be persuaded to revert to pluripotent stem cells, a process called reprogramming. Pluripotent stem cells share characteristics with cells found in the early human embryo that go on to form all the tissues in the body, making them quite unique. Stem cell lines from these embryonic cells had only recently (in scientific terms) been isolated from human embryos in 1998, and the relative youth of the field really appealed to me – I’ve been working with these cells for practically all my research since.
One important reprogramming event is also responsible for all our lives – two highly specialised cell types, eggs and sperm (collectively called gametes) come together during fertilisation, and the fertilised egg regains the potential to form an entirely new individual. The fertilised egg divides rapidly to generate more cells, with each cell type becoming progressively more restricted in its fate during development. Very early on – about 3 weeks after fertilisation – the cells that are fated to form the gametes are set aside. These cells, called primordial germ cells, and their descendants, are how characteristics are passed on from generation to generation.
I study germ cells to understand the causes of human infertility and to identify potential therapies and future treatments.
Current infertility treatments like in vitro fertilisation (IVF) rely on individuals being able to use their own gametes, or those received from donors. But what if infertility is caused by the inability to make gametes in the first place?
One future therapy might first involve making patient gametes. In my lab we can coax pluripotent stem cells to become primordial germ cells by tailoring the signals they receive to mimic those present during development. Patient skin cells could be collected via biopsy, and then reprogrammed to pluripotent stem cells. These could then generate germ cells and eventually, functional gametes that could be used for IVF to form fertilised embryos.
However, one crucial knowledge gap is identifying the signals needed for germ cells to mature.
My work focuses on ovary development, where especially little is known.
This is because eggs are formed during female early development and have a limited supply, unlike sperm, which are constantly produced and replenished during male reproductive life. Studying the signals needed for this to occur is tricky, and relies on a limited supply of donated tissues from very early stages. I’m trying to build a reference map of ovary cell identity, both studying the germ cells so we know what characteristics to aim for when making our own, as well the other cells in the ovary, which are the support network that may provide the signals the germ cells need to mature.
Once we have this reference, we can try and mimic this process in the lab. It’s in the early stages, but no matter how small, every experiment and result means I’m looking at something that no one else may have seen before, which is a pretty good outcome for curiosity.
