For Dr Francesca Froldi, studying development is not only fascinating but it is also vital to better understand and treat diseases such as cancer.
I have always been fascinated by the wonderful complexity of nature. As a little girl my favourite thing to do was to look for insects in my back yard or observe the tiny life forms swimming around in pond water with my toy microscope!
So naturally, growing up, I decided to study biology and become a scientist. During my years at the University of Bologna in Italy I fell in love with developmental biology, the discipline that studies the amazingly complex processes through which a multicellular organism, with all its interconnected and integrated tissues and organs, develops from a single cell.
The development of an organism is guided by the information encoded in its genome. How this information is ‘interpreted’ determines what behaviours or identities its cells, which all share the same genetic information, will acquire.
How this happens remains, in my opinion, one of the most fascinating questions in biology. Indeed, how cells in a developing organism acquire or maintain their identity has become the main focus of my research.
Studying development is not only fascinating but it is also vital to better understand and treat diseases such as cancer.
For example, during normal development unspecialised ‘master’ cells, called stem cells, are able to proliferate and to give rise to progressively more specialised or mature cell types though a process known as ‘differentiation’. Unfortunately, however, differentiated cells can accumulate genetic or epigenetic changes that allow them to turn back the clock and return to a more immature developmental state and reacquire stem cells traits, such as the ability to proliferate.
Deciphering the mechanisms that orchestrate how a cell differentiates is a key question that needs to be addressed, especially if we want to understand the origin of many cancers and find ways to treat them.
Since animal development is so wonderfully complex, studying it is no easy feat! That is why less complex organisms are extremely useful to help us shed light on these intricate processes.
Here at Peter Mac, in the Cheng lab, I use the fruit fly Drosophila melanogaster to study how stem cells in the central nervous system behave and how the neurons they give rise to, acquire and maintain their specialised identity. Through our research, we have found that loss of certain regulatory networks in the fly brain leads to loss of cell identity of these neurons and acquisition of stem cell like characteristics, which ultimately leads to tumour formation. We have also demonstrated that these cancer-causing stem cells in the brain have very specific metabolic needs and that their growth can be prevented by depriving them of specific nutrients without affecting normal brain development.
Given the high degree of evolutionary conservation of these networks and processes between flies and humans, these findings will hopefully inform our search for novel therapeutic strategies for cancers such as glioblastoma which are driven by the activity of cancer stem cells.
Developing Drosophila central nervous system. Stem cells are labelled in red and neurons in green.
Drosophila has been used as a genetic model organism for over a century now, so we have accumulated a wealth of knowledge and numerous tools to manipulate its genome in very sophisticated ways.
Unlike mice, the fruit fly Drosophila is an easy and inexpensive model organism to breed in the lab.
So, it should not come as a surprise to anyone that fruit flies play a role in cancer research (an important one in my opinion!).
Cancer causing mutations were in fact described in Drosophila years before the first human tumour suppressor genes were identified; and it was studying Drosophila development that important signalling pathways such as Notch, Wnt, TGFb, Hippo and many others were discovered, well before we knew what important roles they play in cancer biology.
Developmental biology research in Drosophila is a good example of the importance of fundamental research as it is often the case that discoveries that revolutionise the field of medicine come from studying basic biological phenomena.
And there are many more examples: CRISPR genome editing technology is another striking example that illustrates how studying biological processes that may seem irrelevant to our health, if not a little obscure, can lead to such a huge leap forward in biotechnology. Who would have thought that studying how bacteria defend themselves from foreign DNA would have transformed biomedical research and opened up therapeutic possibilities that were unimaginable only a few years before?
This is why fundamental research should be supported and encouraged: besides being so fascinating, you never know where the next breakthrough in cancer research is going to come from!
Dr Francesca Froldi is a Postdoctoral Fellow in the Cheng laboratory and part of the Organogenesis and Cancer Program at Peter Mac. Her expertise includes Drosophila developmental and stem cell biology and the use of invertebrate models for cancer research.
She can be contacted by email at [email protected]