How does a researcher choose their specialism? Plenty of scientists would struggle to answer the question but it becomes more complicated when other people might not even have heard of the subject you study.
Scientists at the Crick work on hundreds of different diseases and this Rare Disease Day, we're finding out more about the researchers whose fields might be less well-known.
Sila Ultanir: “Meeting patients and parents is incredibly motivating.”
Sila Ultanir leads the Crick’s Kinases and Brain Development Laboratory and studies CDKL5 deficiency disorder (CDD). CDKL5 is an essential protein in typical brain development and it is produced by a single gene on the X chromosome. Mutations of the CDKL5 gene cause neurodevelopmental problems and severe seizures within the first few months of life.
Sila originally came across an article on the gene when she was searching online to see how her knowledge of kinases could be combined with her interest in neurodevelopmental disorders.
She was initially drawn to the scientific challenge. “From a purely scientific point of view, it’s a unique opportunity to work on a single gene disorder, where we already have information about exactly what happens if it is missing.”
The wider community
However, she soon found that the research community around CDKL5 offered much more than just an interesting scientific problem. “Because it’s a relatively small but well-organised community, you have the opportunity to talk to patients and their families and you know exactly what you’re working towards.
“The knowledge that you’re working towards a specific unmet need for these families is a huge motivation to me and my group. Everyone remembers that when experiments get tricky in the lab. It makes the job more meaningful.”
Working as a smaller group also gives the CDKL5 community the opportunity to move faster with their research. Annual meetings organised by the CDKL5 organisation, the Loulou Foundation, bring together an impressive group of patient advocates, scientists, clinicians and pharmaceutical and biotech companies.
It allows CDKL5 researchers, who might be the only person in their group working on the gene, to present their work to the whole community and get immediate feedback from people involved in every stage of diagnosis, management and treatment.
Sila explained how much she values the meetings. “It’s so collaborative. Biotech representatives and clinicians contribute to discussions in amazing ways, scientists share information and reagents and we all move forward faster together. It’s a great way to do science. Everyone at the meeting is constantly aware of the implications of our work.”
Annelien Verfaillie: “I love that I’m able to bring something to the field.”
Annelien Verfaillie is a senior laboratory research scientist in the Crick’s Cancer Genomics group and has worked on MPNST (malignant peripheral nerve sheath tumour) and osteosarcoma, two rare forms of cancer.
She was drawn to the chance to learn new techniques and contribute something new to a relatively small research community. “I found myself working on this by chance. I’m was just totally fascinated by these cancer cells – they are rogue cells which show this crazy behaviour like doubling or quadrupling their genome and they just keep going."
Making an impact
Annelien was originally drawn to the new techniques that she could learn from studying the cancerous cells. Her interest in the diseases themselves gradually grew over time. "I think it’s the other way round for a lot of people. They learn the techniques to work on a disease that they’re already interested in."
Working on rare cancers can give you the chance to address bigger questions. “There are still so many unknowns. You definitely have more ‘oh wow’ moments working on these cancers than you would in a larger research community. I love that I’m able to use my skills to bring something to the field and know that I’m making a difference.”
Rosalyn Flower: “Our work could be applied to more common diseases.”
Hirschsprung’s disease is a congenital disorder that causes a lack of nerves in the end portion of the intestine. In Hirschsprung’s disease, the muscle contractions that should move stool through the bowel cannot occur in the affected region and surgery is required for the survival of every patient.
80% of patients with Hirschsprung’s disease are male but the underlying cause of the sex bias hasn’t been found yet. “By studying Hirschsprung’s disease, which has such a distinct difference in frequency between sexes, we can create a model to study sex differences more broadly.
"If we understand how sex chromosome genes and sex hormones affect Hirschsprung’s disease, our work could be applied to more common diseases that also show differences between sexes.” says Rosalyn. “This includes a huge range of disorders; things like Alzheimer’s disease, multiple sclerosis and depression.”
Sex differences in diseases have been overlooked in the past but could hold vital information about the basic mechanisms of diseases. Rosalyn explained that even policies and regulations are only just starting to acknowledge sex differences in diseases, “The National Institutes of Health only recently mandated that scientists have to report the sex ratio of mice used in experimental studies."
Up until a few years ago, the vast majority of mice used in some fields, notably neurobiology, were male. Female mice weren’t used in some studies because of concerns about variability due to their reproductive cycle.
"This is missing the point. This variability is normal and needs to be considered in experiments," says Rosalyn.
“It wouldn’t be a stretch to say that the use of male mice could be one of the reasons why treatments that show promise in mouse models fail at clinical trials. By acknowledging that this is important, it shows that people are beginning to recognise the importance of sex differences.”