Meet the Expert: Teresa Niccoli

Question 1: What inspired you to specialise in the field of dementia research and how did you start working with fruit flies?

Answer: I started working with flies during my first post-doc in Daniel St Johnston’s laboratory at the Gurdon Institute in Cambridge. I was studying cell polarity in early development, using Drosophila oocytes as models. I really enjoyed working with flies but wanted to work on a topic more directly related to human health. Dementia is the leading cause of death in the UK and yet it remains a very under-researched area (compared, for example, to cancer).

We still understand surprisingly little about how the disease starts and how it develops, this provided scope and opportunity to develop my research into areas of interest and hopefully contribute something of value to the field. Also, the dementia research community is characterised by strong collaborative links between clinicians and basic scientists, especially so at UCL. This leads to very fruitful exchange of ideas and steers research into a direction that is more directly linked to disease, which I value.

Question 2: You’ve taken career breaks. Do you think all academics would benefit from doing this, and what advice would you give to anyone wanting to do the same? 

Answer: I took one 5 year career break, starting when my first son were born. I never regretted it, I got to spend valuable time with my sons when they were small and experience life at a very different pace. For me, taking a break meant I could concentrate on enjoying being a new mum, with all its challenges, and getting used to a totally new baby-oriented routine, without the stress of worrying about how that affected my work performance. Once the children were a little older and I had a good home routine in place, re-introducing work was a less stressful experience. 

It’s not for everyone, having only a toddler to talk to for most of the day can be challenging! However, if someone wants to take a career break I would say not to worry about not being able to get back into science. There are many funding opportunities for parents returning to work, and employer are increasingly willing to take on parents who have been on a break. It does go without saying, but the better your CV when you take a break, the easier it is to get funding when one decides to come back, my advice would be to make sure projects are competed and published ahead of a break.

Question 3: What area of your work most excites you and why?

Answer: Neurodegenerative diseases are all characterised by the death of brain cells. However the clinical symptoms first experienced by patients vary depending on disease, Alzheimer’s disease patients experience memory loss, whereas patients with Motor Neuron Disease lose the ability to move. This is linked to which type of brain starts dying first. One of the big challenges in the field is understanding why only certain brain cells die in a particular disease. Why can Alzheimer’s patients not remember where their keys are but can walk just fine? 

A new technique has recently been developed called single cell sequencing, this allows researchers to look at the response of each individual cell to a particular environment. Analysing in detail cells that die and cells that don’t, in a particular disease context, will hopefully allow us to understand more clearly what is causing the demise of particular cell type. We will be trying this in our fly models of dementia, and hope to gain novel insights into how these devastating diseases develop.

Question 4: You’ve worked with Paul Nurse and Linda Partridge. What did you take away from your time with them? 

Answer: Both Paul and Linda are very inspirational scientists, and it is a privilege to have worked with them and to still be able to benefit from their insight and vision. I have learned a lot from them. A couple of the most important things I have learned is that one should always be open to question their theories and assumptions when data doesn’t quite fit, and the importance of a good, well controlled experiment. I have also learned that interesting discoveries can come from the most unusual places, therefore one should never dismiss “odd” observations.

Question 5: The work of the Institute of Healthy Aging is producing some exciting work. Which project are you most proud of?

Answer: The Institute of Healthy ageing, from its inception, has contributed some major insights into ageing and diseases linked to ageing, by working on a variety of model systems. One of the projects I was directly involved in, as a post-doc, was a collaboration between Adrian Isaacs at the Institute of Neurology (at the time) and Linda Partridge. We established fly models of a mutation causing Frontotemporal Dementia and Amyotrophic Lateral Sclerosis which had just been identified. Together with Sarah Mizielinksa in Adrian’s laboratory and Sebastian Groenke in Linda’s lab in Cologne we generate and characterised these new models.

This collaboration was a perfect example of how combined expertise from three senior post-docs, in different laboratories, working very closely, can yield a publication of major interest in a timely fashion. In less than 2 years we published a paper in Science, describing for the first time why the mutation was toxic. These findings have now been replicated in a number of models, including human cells. I learned the power of good collaborative research and this was another example of how invertebrate model systems, like Drosophila, have a lot to offer to medical research.

Question 6: How has the pandemic changed your work, and how have you and your team coped?

Answer: In March 2020 when the UK shut down, we had to bin all on-going experiments and drop to a minimal maintenance regime of just keeping our of fly stocks alive. Flies can’t be frozen and the Institute’s collection houses thousands of lines, so someone had to come in to feed the flies throughout the pandemic. 

Stopping everything so quickly was difficult, it took one year to be able to set up again the same experiments we had running at the time, as the type of experiments we run require long preparatory work. I became an independent lab head the year before the pandemic, and so ended up building my group during lock-down. Most members of the lab started in the last year or so, when we were working in shifts with distancing requirements in place.

Building a social rapport within the group, when half the group could not meet in person the other half as they were on different shifts was challenging. Training newcomers and brainstorming of new ideas is very difficult over Zoom and with distancing requirements in place. I am very proud of how all members of the group pulled together and made the most of a far from ideal situation. We are now, gratefully, almost back to normal, slowly all social interaction are returning to pre-pandemic routines. These are important to build a sense of belonging and it is what makes working at the IHA so enjoyable.

Question 7: What’s your next big challenge in terms of your research?

Answer: The lab has received funding from the Alzheimer’s Society to look at the effect of the drug metformin on the development of Alzheimer’s disease (AD), in collaboration with the laboratory of Selina Wray, at the Institute of Neurology. Metformin, a drug used to treat type diabetes, can increase the lifespan in a variety of species, suggesting it interacts with conserved pathways relevant to ageing. Epidemiological studies, however, have given conflicting results as to its efficacy in AD.

We have shown that metformin can dramatically improve the symptoms of a fly model of disease, We have evidence suggesting it might be making neurons better able to deal with the presence of toxic elements linked to disease. This project will work out the molecular details of how metformin is doing this using our fly models. We will confirm this in human neuronal cells derived from patients. This project should help develop more specific drugs for AD, and identify novel mechanisms of disease, potentially linked to ageing. 

It's exciting because it’s the first time we have directly worked on the development of a therapy for Alzheimer’s disease, and we look forward to showing the power of combining Drosophila genetics with human cell models for the development of therapies.

Further information:

• Dr Teresa Niccoli staff profile
• Alzheimer's Society
• UCL Institute of Healthy Ageing
• Niccoli Lab
• Research Department of Genetics, Evolution and Environment
• UCL Queen Square Institute of Neurology