Lockdown has not stopped science

The new coronavirus pandemic and the global lockdown it caused had an unprecedented effect on everyone around the world, no matter the occupation. Our lab-based projects ground to a halt in early March, forcing us to come up with more creative ways to tackle our scientific interests from home. How do we continue to do our research during the lockdown?

Matt, usually busy running drug-screening experiments to find drugs that may benefit ALS patients, focused on mining extra information from his existing data. “In normal times, looking for new ALS therapeutics requires many hours in the laboratory, access to cutting edge equipment, and growing patient-derived cells. In lockdown, I could not continue this lab work, but I could go back to data collected earlier in the year to identify new features that we could use as indicators of neuroprotection and make the drug screening assay more efficient and informative.”

Drug screening experiments being analysis.

“Here is an example of the data from a drug screening experiment I performed before lockdown. Motor neurons are grown with ALS patient iAstrocytes ‒ which are toxic. I treat these cells with a range of drugs, and look for drugs that increase the motor neuron survival. Here, the blocks coloured in red only have a few motor neurons, whilst the blocks coloured in green have lots of motor neurons and indicate the drug may be beneficial for ALS patients.”

Nora, who is on the same project as Matt, also mostly focused on improving the data analysis of experiments run before lockdown.

Patient-derived motor neurons.

“Above is an example of ALS patient-derived motor neurons, which have been treated with medium derived from ALS patient iAstrocytes, which are toxic. Drugs, which have shown to increase motor neurons survival in our previous experiments were added to the cells to see their effect on different aspects of cell function. The images are analysed using the help of a software called Harmony®. The aim is to further understand how the drugs, which we are testing as potential ALS therapeutics, exert their action. The results of these experiments will give us a clue as to what causes the protection of motor neurons we see with our drugs, which will help us advance these drugs towards the clinic. “

Similarly to Matt, Lai Mei would normally be running drug-screening experiments in the lab, working on projects with our industrial collaborators. However, with lab work on pause, she has also spent part of her time analysing data she collected prior to lockdown. “Here, I am using a programme called Columbus, an image analysis system to look at motor neuron survival. We can use this programme to count numbers of healthy motor neurons, as well as to measure several other parameters indicators of neuroprotection, following drug treatments”.

Analysing motor neuronal survival using Columbus software.

“Additionally, I have been working with Chloe and her RNA sequencing data, looking at gene activity and deducing the mechanisms of action of drug compounds. Working remotely has been challenging, especially when the majority of the work we do takes place in the lab, but together we have adapted well to find ways to continue our research”.

Jannigje and Cleide, both working together to deconvolute the molecular mechanisms behind oxidative stress response in ALS motor neurons, took this unexpected opportunity to expand their scientific horizons and training by attending online training courses. “While lockdown has prevented us from making progress with experiments, it has provided us with several opportunities to develop new skills that we needed to progress our projects in the future. 

One of the courses Cleide and I were able to attend was an online class teaching a cutting-edge technique for manipulating cell genetics, called CRISPR. 

Over a period of two days, we attended seminars and workshops to learn more about the technique and how to apply it to our own experiments. Once lockdown is lifted, we will be able to use this technique on the cells we have obtained from ALS patients with genetic causes of disease. This could allow us to correct the affected genes, and see whether that reverses the patterns of disease the cells exhibit and, therefore assess whether removal of toxic genes from cells is beneficial after disease has started.”

How can CRISPR technology be used in ALS?

Similarly, our 1st year PhD student Ana has been attending a lot of online training courses and webinars, missing no opportunity to ask questions.

We were not only attending online events – we were organising them! Communication within the scientific community is key for the progress of research. Not only it is an opportunity to be exposed to cutting edge unpublished findings, but it is also a fantastic occasion to exchange ideas with other scientists, so that we can move forward in our search for a treatment faster and with new ideas. 

This year’s edition of FENS took place solely online and Cleide and Laura organised a very successful symposium on glial cells in neurodegeneration. Congratulations!

Dr Laura Ferraiuolo at FENS 2020, opening the satellite event on the role of glial cells in the era of personalised medicine.

Although the lockdown has prevented us from running experiments, it has not stopped the assessments and career development of 2nd year PhD students like Janny and Marco. “As PhD students, our studies and assessments have been continuing during lockdown. In the second year of our PhD we are expected to prepare a poster displaying our research for the annual University of Sheffield Medical School Research Day. This is usually a great event where students and more senior scientists get to share and discuss their research, often gaining new perspectives and ideas to take forward. 

Of course, because of COVID-19, the Medical School Research Day was cancelled. It was decided however, that the assessment would still go ahead albeit with some modifications to adapt it to a new online format.

For the assessment, we were required to prepare a research poster and record ourselves presenting the poster as if to an audience. Due to the lockdown and not being able to work at the lab, there was plenty of time to do both, although it must be admitted that recording yourself giving a presentation is a bit of an odd experience.”

Janny at her 2nd year PhD poster presentation

For our 3rd and 4th year PhD students, the lockdown means devoting all attention and energy to thesis writing. Noemi even managed to submit her thesis and has had a one-of-a-kind experience of going through a lockdown viva at the end of July. Well done Dr Noemi Gatto!

The thesis shall be conquered!
Mouse the cat ‘helping’ Allan put together his data presentation.

Allan is coming to the end of a project investigating a gene that can cause both ALS and frontotemporal dementia using astrocytes made from the samples kindly donated by patients with the diseases. “Unexpected stops to lab work are always challenging, this time especially so as I had made some exciting breakthroughs in my research and had several months of experiments planned. Despite this, I enjoyed the transition to working from home. I had time to put my work into context, begin writing up my findings so that I can share my research with other scientists and improve on my experimental plans. The other delightful benefit from working from home is spending more time with my cat, Mouse. She loved supervising me, joining (or getting in the way!) in meetings, and reminding me when to take a break (mostly to give her treats).”

“Outside of working I took the time to appreciate the glorious spring more than ever before. I have also been running around, raising charity funds for a similar project to my own but focused on finding cures for Parkinson’s disease. I was due to run in the Sheffield Half Marathon in late March but this will now take place in September. I’ve continued my training throughout the lockdown and hope to raise even more in the coming months!”.

Chloe has also been writing her thesis, while ploughing through spreadsheets full of RNA sequencing data she has gathered during her PhD. This kind of analysis takes months-worth of hours of computer work. “In my project, I have been using astrocytes to try to find new drug treatments to help motor neuron survival in ALS. Image the brain as a beautiful garden, if the motor neurons are the plants, then the astrocytes are the gardeners. It is their job to help keep the motor neurons healthy. In ALS, the astrocytes do the opposite of this and cause harm to the motor neurons. So, we are looking at drug treatments that stop the astrocytes from being bad gardeners!

The activity of the genes in our body are very important for our body to function normally and stay healthy. I have been using a programme called DEGUST, this allows me to look at differences in gene activity between an astrocyte with an ALS genetic mutation and a healthy astrocyte. I can also look at changes in gene activity between an astrocyte treated with a drug compound and an astrocyte that has not received any treatment. 

Using DEGUST, I can create a visual map, called heatmap, which shows me these changes in gene activity. On this heatmap, genes that are more active are in red, while genes that are being switched off are in blue. We can use this heatmap to identify genes that are changed after treatment to understand how a drug works and which patients should take the drug based on their gene activity.”

DEGUST software helping Chloe map the genetics of patient astrocytes.

Similarly, Monika has been dividing her time between thesis writing, data analysis, and writing a review paper on uses of artificial intelligence techniques in neurology and neuroscience. “We live in an information age where, as scientists, we get to see hundreds of research papers across many disciplines published on a weekly basis. We cannot possibly read all the information that’s out there in our lifetime! Natural language processing-driven machine learning algorithms can do it for us, whilst also coming up with scientific hypotheses for us to test. My PhD revolves around understanding how two drugs, which AI has suggested might work for ALS patients, affect astrocytes and how they work in the context of ALS. For example, I have been analysing the effect of these drugs on the rate of astrocyte growth and their shape, which can itself provide a lot of information about the pathways these drugs modify”.

Monika with her article on the uses of machine learning in neurology.

She has also been working on a very interesting review article: “I developed a keen interest in machine learning and its uses in medicine during my project. I have collaborated with BenevolentAI to put this article together, which you can now read online!”. Also, Monika has been designing the very website you are reading this post on. We hope you like it!

We continue to hold weekly lab meetings, which have now turned partly into show-and-tells. Our lab members have a diverse range of skill sets, experiences, and interests which they don’t often have an opportunity to showcase, hence we have been delivering short talks during lab meetings. Janny and Monika, for example, delivered a seminar on public engagement and outreach, where they not only talked about their experiences, but also gave advice and tips to colleagues looking to get involved in volunteering activities. Marco has delivered a presentation about the work conducted by technicians working with more complex in vivo models, Chloe presented an overview of a career management course she has attended, whilst Laura has given us a tutorial on academic writing styles, which we all need for our future as scientists!

Monika delivering a seminar on public engagement and outreach.
Janny teaching us how to write a scientific article for a lay audience.

But all work and no play makes the Ferraiuolo lab a dull bunch. Seeing as we cannot socialise the way we used to, we keep up the morale by having online socials and quizzes, such as the one organised by Ana, where she put our knowledge of fine arts to the test.

Even though we all navigate very uncertain times, researching neurodegenerative diseases and looking for cures does not stop! And neither do we want it to. 

Stay safe!

The Ferraiuolo Lab

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