Dr. Fanucchi, tell us what brought you to biochemistry and cell biology? Was this a childhood dream becoming a reality, or was it something else?
For as long as I can remember, I have been curious about the natural world. In high school I remember being intrigued by biology and chemistry lessons, while the majority of my classmates appeared to be highly disinterested and bored! Although I always had this passion for biology, I considered pursuing many different career paths, and I never dreamed that I would end up becoming a scientist. But, I am incredibly fortunate in that my husband and family strongly encouraged me to follow my passion and study biochemistry and cell biology. I am very grateful that they did, and I feel very lucky to have found a career that I love.
You have been recognized as a Rising Talent by the 2017 L’Oréal UNESCO for Women in Science programme. How much does this award mean to you, and why is it important for your future career steps?
I was stunned and speechless when I heard I had been selected to receive such a prestigious award. While science is such a rewarding career, it can at times be extremely frustrating. Receiving such an award gives me the much needed confidence to continue pursuing my scientific career. My dream would be to run my own lab, or to be involved in a biotech startup company. My hope is that receiving this award will help make these dreams become a reality.
You were part of a team of South African researchers who published a ground-breaking study about gene regulation in Cell, one of the world’s most prestigious research publications. Tell us more about the key findings of the study.
In almost every cell of the ~1 billion cells in the human body, there is a nucleus that contains DNA, your cellular blueprint. If you removed all the DNA from each nucleus, and stretched it out, it would form a string greater than 1 meter in length. This DNA has to be packaged to fit inside the nucleus, which is one-fiftieth the size of a grain of sand. As such a large quantity of DNA is packaged in such a small space, regions of DNA are permitted to interact or “kiss”. In the 2013 study, we showed that these “gene kissing” interactions were important to the regulation of interacting genes. This study, combined with many others, revealed that we need to carefully consider how the folding of DNA in the nucleus impacts how genes are switched on. This is especially relevant in processes, such as inflammation, which are ultimately controlled by how immune genes are switched on and off.
Part of your research includes finding out how immune genes are regulated. For this you use cutting-edge microscopes and synthetic biology tools. Can you tell us more about the term synthetic biology?
Synthetic biology is an exciting and rapidly expanding new field of research which is revolutionising our understanding of biological processes. In essence, synthetic biology is the application of engineering principles to biology. Discoveries in this field are driven by advances in the ‘synthetic biology toolbox’. Some important tools include the ability to program ‘molecular scissors’ to make discrete changes to DNA or the ability to use highly specialised microscopes to visualise single molecules, such as DNA. In the future, I think these tools could prove to be very useful in the treatment of many diseases. For example, scientists are attempting to use molecular scissors to correct mutations in different disease states, such as Duchenne muscular dystrophy and several cancers. Although scientists are still cautious that these therapies may cause unintended side effects, clinical trials using these technologies in adults and children with leukemia or lymphoma have yielded optimistic results. Therefore, synthetic biology has the potential to radically improve how we treat many types of cancer and chronic diseases.
Do you think that if, in the future, you manage to reveal the mechanisms of cellular processes and immune genes behaviour, we will be able to treat cancer or chronic diseases such as diabetes?
Yes, I believe that once we have a detailed understanding of these processes we will be able to develop much more effective therapies to treat cancer and other chronic diseases. If your mechanic has no idea how a car engine works, it's highly unlikely that he will be able to fix it when it breaks. The same is true for cells and disease. If we gain a detailed understanding of how cells function we will be able to understand what goes wrong during disease, so we can come up with novel therapeutic strategies to cure diseases, and not just treat symptoms. But… this is easier said than done!
Your work focuses on understanding how inflammation is controlled at the level of gene regulation. If you manage to find that balance where inflammation is at just the right level, how would this discovery impact the lives of people in general?
Inflammation is a so-called double-edged sword, you need it to clear infection, but if it is not precisely regulated it leads to a multitude of diseases, such as cancer and autoimmune disease. In a normal immune response, the body is able to precisely control the inflammatory response. However, in the case of sepsis and other inflammatory disorders, this process is not properly regulated leading to the uncontrolled activation of the immune system and exacerbated levels of inflammatory processes. In these circumstances, the immune cells are not only targeting the infected or diseased tissue, but healthy tissue as well, leading to lethal consequences. Therefore, I believe that the ability to intervene and dampen excessive inflammation will have a major impact on human health.
Can you tell us more about how you perceive the correlation between the immune system and development of cancer in the human body?
Every year, more than 14 million people worldwide are diagnosed with cancer. In many instances cancer is caused by an error in your DNA, or genetic code. These ‘errors’ or mutations can be passed on through generations and are one of the reasons why your chance of developing cancer is so much higher if you have a history of cancer in your family. Even though you may be predisposed to develop cancer, your body still has a natural defence, called the immune system, which can attack and kill cancer cells. However, cancer cells are able to ‘hide’ from the immune system and in doing so are able to escape being eradicated by immune cells. Therefore, there is an intimate relationship between altered immune function and cancer development.
Recently, some exciting therapies are able to ‘unmask’ these immune cells so they are able to recognise cancer cells to kill them. In some patients these therapies have resulted in the successful reactivation of the immune system to kill the cancer cells. Unfortunately, this is not always the case. In other patients, immunotherapy leads to the over-activation of the immune system, elevated levels of inflammation, and death. Clearly, while these approaches are very exciting, further research is required to refine these therapies.
Do you think that cancer has anything to do with the genes we are born with and that we are, in a way, predetermined to have more chances to become ill only because some members of our family had cancer in the past? What does science have to say about this?
Yes, mutations or errors in your genes will have a major impact on whether you may develop cancer. For example, a large percentage of women who possess a faulty copy of the BRCA1 gene will develop breast or ovarian cancer. It is for this reason that the actress Angelina Jolie decided to undergo surgery to reduce her risk of developing these cancers. However, it is important to note that cancer is a multi-factorial disease, with multiple causes. Recently it has become very clear that environmental factors (diet, pollution, radiation etc.) are major contributors to the development of cancer. Environmental factors can alter the ‘openness’ or state of your DNA. If DNA is in a more ‘open’ state it is more easily converted into a message, which is called RNA. The study of the state of DNA is called “epigenetics”, and it represents an entirely new way to understand how cells function. Some recent studies suggest that the ‘epigenetic code’ may be an excellent predictor of lifespan, disease risk, and even how a patient may respond to cancer treatment. While we currently can’t do much about mutations that we inherit, it appears that your epigenetic code may be improved by altering lifestyle habits, e.g. stopping smoking. We are in the era of personalised medicine, and, in the future it is highly likely that we will be able to use an individual’s genetic and epigenetic code to guide how we diagnose and treat disease.
What are you striving for in science? What would you like to be remembered for 20 years from now?
As a scientist, you are evaluated by how many high quality patents and publications you produce. In order to generate impactful research you need to do hundreds of experiments, read hundreds of research papers, discuss these papers with other scientists to come up with new ideas and travel to conferences to present your data. In addition, you need to try to find a way to compile all these ideas and data into manuscripts, which are peer-reviewed and may require years of refinement before publication. All of this takes a lot of time and energy, and science moves forward very quickly. Therefore, there is a considerable amount of pressure to continually be innovative, accurate and perform at a very high level. So in my scientific career I am striving to do the best I can, and I really hope that my work may have an impact on how we diagnose and treat disease. Personally, I think I would like to be remembered for being relentlessly curious, passionate about life, and developing future scientists.
Photo credits: Laurianne Davignon