Debora's early curiosity and education
Born in Italy to a Swiss mother and Italian father, Debora has always had a strong curiosity. For example, at a young age she wanted to know why rainbows form in the sky and why other phenomena happen. But she did not really consider studying science until she was 16 when she had an 'amazing chemistry teacher'. Prior to this she had always been encouraged by her teachers to pursue humanities subjects because she was good at it.
So inspired was Debora by her chemistry teacher that she decided to take the subject at La Sapienza University in Rome. Going this route was not easy for Debora because most of her school studies had been in the humanities. As a result her first year at university involved a lot of catching up. But she did not mind because she 'really enjoyed it' and she had found her real passion.
After completing her chemistry degree at La Sapienza, Debora did a doctorate in structural biology at the European Molecular Biology Laboratory (University of Heidelberg) in Germany. Her research concentrated on DNA regulatory enzymes which play an important role in turning genes on and off. She continued looking at these enzymes as a postdoctoral researcher at Cancer Research UK.
First step into industry and witnessing a new approach to DNA sequencing
In 2009 Debora became a research scientist at Oxford Nanopore Technologies (ONT), a spin-out company from Oxford University developing a new form of DNA sequencing technology called nanopore sequencing. Founded in 2005, the company was still relatively new when Debora arrived there and was still in the process of proving nanopore sequencing could work.
At this point the DNA sequencing market was largely dominated by a small handful of Californian companies funded by venture capital. All of these companies produced the same sort of systems based on sequencing by chemical synthesis. One of the major problems with this was their sequencing machines tended to be very expensive and very large so could only be purchased by well-resourced laboratories based in higher income western countries.
Nanopore sequencing offered a radically different approach which had the capacity to make sequencing much faster, cheaper and more portable. Critically it was designed to work out a sequence by monitoring unique electric signals given off by different nucleic acids as they pass through a nanopore, a tiny hole one billionth of a metre in diameter. This approach had several benefits over previous forms of sequencing. Firstly it did not require a sample to be initially amplified to carry out sequencing. Secondly, it made it possible to read a sequence from a biological sample in real-time.
Debora was hired by ONT to manage a team researching DNA processing enzymes. She oversaw the initial stages of the project and its development and applications and helped see it get translated into manufacturing. Remaining with ONT for just over two years, Debora learnt an enormous amount about building a company and felt incredibly fortunate to see upfront how an idea developed in the laboratory could be transformed into a marketable product. What she also really liked about working at ONT was the passion and vision of everyone at the company. The experience was incredibly inspiring for Debora and she says it opened her eyes to the possibility that one day she might be able to do something similar. It also taught her the value of basic scientific knowledge for innovation.
Returning to academia to study the genetic risks of disease
After ONT, Debora joined the MRC Epidemiology Unit at the University of Cambridge. Appointed first laboratory manager and then head of MRC-Epidemiology laboratories and NIHR BRC-MRC BioRepository, which collects, processes and stores thousands of human biological samples taken from volunteers, including DNA. The biorepository acts as a resource for biomedical researchers, such as epidemiologists who study how often diseases occur in different groups of people and why. One of the most powerful ways of doing this is to track the health of large groups of people over time, known as large population studies. An important part of this process involves studying how genetic factors contribute to health and disease in families and populations and looking at the interplay between genes and the environment. This can help uncover particular genetic markers associated with certain diseases like cancer and diabetes which are useful for prevention and treatment.
One of the research areas the MRC Epidemiology Unit was exploring was how obesity, type-2 diabetes and related metabolic diseases were affected by genetic, developmental and environmental factors. In order to do this they and their collaborators investigated over two million genetic variants in almost 200,000 people to look for links to insulin resistance. Over a hundred researchers worked on the project, including doctors, scientists and data analysts. They found that 53 regions of the genome were associated with insulin resistance and raised the risk of diabetes and heart disease.
As part of her work in the Epidemiology Unit Debora began looking at different technology platforms to support large-scale genetic-based research studies. The starting point for such investigations involves extracting DNA from thousands of blood samples and then preparing and analysing the DNA and correlating this with other data such as environmental factors like a person's lifestyle and diet. In order to make this process more efficient Debora and her team looked at automated systems that would make it easier to perform high-throughput DNA extraction and measure the quantity of pure DNA obtained. Getting these steps right are crucial to making sure the genetic analysis down the line produces reliable results. Debora really enjoyed developing the tools which made it possible to study many thousands of samples from patients and healthy individuals in more detail.
Diving back into the commercial world
After spending nearly six years at the Epidemiology Unit, Debora realised that she really wanted to get some more experience of working in the commercial environment. As a result she accepted a position as director of biomarker discovery at Cambridge Epigenetix, a company focused on pioneering sequencing tools to better understand epigenetic changes to DNA. These are chemical tags that get added to DNA which help switch genes on and off. Such modifications do not alter the underlying DNA sequence, but are key to regulating gene expression, the process that governs the production of proteins. Epigenetic changes underpin normal cellular development and help distinguish one cell and another. Any disruption to this process can cause disease.
Remaining at the company for just over a year, Debora oversaw the development and testing of its technology to detect hydroxymethylation, a type of DNA modification associated with the development of cancer. As part of this work she led a project designed to test out the technology for diagnosing colorectal cancer. This involved investigating over 2,000 patient samples, including healthy volunteers and patients with different stages of colorectal cancer, to identify a consistent marker that would make it possible to diagnose the early onset of cancer. Debora says she will never forget the moment when she saw for the first time the cancer signal flick up on her computer screen. Seeing this after months of work was especially momentous for her because the marker provided a means to develop a minimally invasive blood test that could screen for the disease before patients showed symptoms. This is key because treatment tends to be more successful the earlier cancer is spotted.
Heading up a spin-out company
After spending 16 months with Cambridge Epigenetix, Debora felt ready to take on another challenge to head up Enhanc3D Genomics, a spin-out company founded in 2020 on the back of a new 3D genomics platform pioneered at Babraham Institute in Cambridge. The platform integrates molecular biology technologies with machine learning to map the 3D structure of the genome at high resolution. What was promising about the technology was it had the capacity to uncover previously unseen genetic markers. It also could decode very large genetic variation datasets into novel disease mechanisms. Debora was very excited by the platform because she could see its potential to become a tool to help physicians tailor therapeutic interventions to each individual and optimise their care and treatment management.
When Debora joined the company as Chief Executive Officer in May 2020, it was still very much in its infancy. Her first challenge at that point was to raise funding. This was not an easy task. Essentially the key challenge was getting the message right so that investors could be persuaded to support the company. As Debora argues 'you could have the smartest idea in the world, but if nobody understands it then it is not going to go very far.' At that point, she says, 'I was very grateful for my humanitarian studies in my early years and for my parents being able to speak four languages because those skills came into play.' Importantly it enabled her to communicate complex scientific ideas to people without a scientific background and for whom English was not their first language. But what also really helped her persevere through the first tough months was she really believed in the idea.
Debora has now been leading Enhanc3D Genomics for three years. Taking up the position just as the effects of the COVID-19 pandemic began to hit, Debora says it was initially a huge shock to her system. But she has no regrets. As she says, 'it's been an amazing experience. I have met extraordinary people along the way, really smart people, scientists, investors, commercial people.' What she loves about her job is every day she gets to learn from other people and find out something new. Having their support has been crucial not only in terms of raising finance but also giving her scientific credibility.
'It takes time to find your real love in life'
When asked what tips she would give to others wanting to pursue a career in the biomedical sector, Debora stresses 'it takes time to find your real love in life'. In her case she went in and out of academia and the commercial world until she found what was right for her. Along the way she has experienced lots of different types of work, all the way from experimenting at the benchside to shepherding a laboratory innovation through to the clinic. Each of these has taught her new things and helped move her forward.
Debora also emphasises the multidisciplinary nature of science and opportunities for people with a range of backgrounds. For example, her training in humanities proved enormously helpful to her when it came to communicating the excitement of science to raise funding. She also highlights how much biology is now blended with artificial intelligence and degree to which medicine is now reliant on technology. This means there is scope for people with lots of different talents. Only by talking to lots of different people and trying out different environments, Debora says, will 'you understand what you enjoy, have a passion for and what drives you.'
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This article was written by Dr Lara Marks based on an interview conducted with Dr Debora Lucarelli on 14th July 2023.