Have you ever wondered what the day-to-day looks like for the Specialised Laboratory teams who analyse our DNA with cutting-edge genome sequencing processes?
For those of you who are not experts in science, our conversation with Rare Disease RNA Phenotyping Project Manager Natasha Morgan and Head of Sample Management Kathy Stirrups gives us an insight into just that!
Find out about how the role of the Specialised Lab teams ties in with the overall activity of the BioResource, their daily processes, and challenges they face along the way.
Can you tell us about the role of the Specialised Lab teams at the BioResource?
The Specialised Lab teams were set up so that they could develop complex and specialised scientific experiments and then process samples identified by clinicians using these methods. It adds a great breadth and depth to the knowledge that we have and is looking at cutting-edge technology and how it can potentially be implemented into a health service. We have several Specialised Lab teams set up across the country so that we are able to provide a national service for the BioResource projects that are currently being run. These are based in Cambridge, London and Leeds.
What does a regular day look like for the Specialised Lab teams? Are there any key projects you're working on?
A day in the lab always consists of processing samples and trouble shooting.
There are two main projects running through the labs at the moment: The Rare Diseases RNA Phenotyping project (RDRNA) and the new Long Read Whole Genome Sequencing project (LRWGS).
The RDRNA project has been running for a couple of years now and is in full swing. Clinicians apply for their rare disease projects to participate, if the application was successful the clinicians identify the patients that are eligible. After two rounds of applications there are now 17 different rare diseases participating in the project.
How it works? A recall appointment is made, where 50mls of blood is donated, this is then couriered directly to the lab. We process the samples on the same day, which is essential as the blood starts to change as soon as it leaves the body and we want to take a snapshot of the participant at that moment in time. In the lab, whole blood is stored down which will be used for short read whole genome sequencing, then specific blood cell types are isolated – monocytes, T cell helpers, neutrophils and platelets. These are used for RNA sequencing and proteomics analyses, which lets us know what genes are turned on in each cell type. We also store down additional samples for other processes. All in all, we end up with 13 data sets per patient, which is an enormous amount of data which then needs to be analysed. Due to the complexities of the technique, it takes around 4 to 5 hours for two people to process up to 4 patient's blood samples at a time. Each patient is different and so is each blood sample, so it often involves the lab thinking on their feet and tweaking the experiment protocol to get the best results possible. It also takes great teamwork, as you have to work closely together and know what each other is doing to ensure everything runs smoothly. On subsequent days the team prepare the DNA, RNA or cell extracts ready for genomic or proteomic analysis.
The LRWGS project is new, still in the pilot phase, with the aim to determine the benefits of a new sequencing technology, Long Read Sequencing, in three of the BioResource research areas; Rare Diseases, Eating Disorders and pre-symptomatic detection of dementia. New equipment is being used and all the experiments are still being piloted and tested before it gets approved and patient samples are processed. This involves doing lots of smaller experiments to see what works and what doesn’t work, to make sure that when we process patient samples we will get good quality consistent data.
Long Read Sequencing technology has the potential to provide additional detail when analysing genomes, particularly for complex structural variants and repeat regions which may be poorly mapped using the current technology. The team have been installing some new equipment in the lab and optimising the DNA for use in this new technology, then we aim to scale up and sequence thousands of genomes over the next year. This will generate a large scale Long Read Sequence genome resource that many researchers will be able to benefit from and yield new insights into many different disorders.
Which other teams do you collaborate with at the BioResource?
We work with many teams, both within the BioResource and external partners. From colleagues in the Samples team who book in patients, the Nursing teams across the country who conduct appointments, the Data team for compiling lots of data and undertaking analysis as well as many others; without collaboration these projects wouldn't be possible, so, thank you to everyone involved.
What is the most rewarding aspect about working in your team?
Knowing that the work we do will hopefully make a difference to someone's life. For both projects the patients that participate have a rare disease. They might have been on a long journey to get to this point in the first place with lots of referrals from department to department. They may still not have a definitive diagnosis. Through these two projects we hope that for some we will be able to help provide a diagnosis or an understanding of their rare disease. Every sample we process is precious, it has been donated by a patient, we are very grateful and process it with the utmost care.
Three phrases to describe the Specialised Lab teams...?
- "Ambitious science."
- "Fun teamwork, where rock-paper-scissors is used to resolve most things."
- "The team that always has the radio playing in the lab and KitKats at the ready."
Finally, what is the most challenging part of your role?
There is always some unexpected complication to overcome within the labs. This could be a courier delay so the samples arrive late which may mean a late working day to get everything done in time. All the way down to ensuring that general lab management is kept on top of so that we don't run out of gloves. A curve ball that gets thrown our way is the rain, when you cycle into work and it suddenly downpours this can result in very soggy lab staff.
A huge thank you to Natasha Morgan, Kathy Stirrups and the team for this valuable insight into the workings of Specialised Laboratory teams.
Researchers can find out more about using the NIHR BioResource or make an enquiry by contacting us via nbr@bioresource.nihr.ac.uk.
Anyone can join the general population BioResource, whether you have a health condition or not. Find out more about how to take part!