ELRIG Research & Innovation 2018 – Day 2
Disease is a journey to work!
Following a fabulously informative and inspiring day 1 which was focussed on oncology research, ELRIG’s Research and Innovation conference day 2 looked at neurosciences with speakers from GSK, Storm Therapeutics, Astex Pharmaceuticals, Sygnature Discovery and the universities of Cambridge and Oxford amonst some who shared their research and described new approaches.
Let me start at the early stages of the familiar research path: identifying the correct cell line to work with. Caleb Webber from the Henry Wellcome Centre for gene function at Oxford University described disease as a journey to work and used the analogy to ask if we are looking at the correct targets for new treatments.
Imagine the life cycle of a cell as your daily commute to work where the cell is your car and the journey represents cell development. Correct cell development would see you leave home on time and arrive at work on time without incident. Correct cell function would see you accelerate, change gear, negotiate roundabouts, and park to allow you to get to work safely. But, on any given day you leave home as normal, get halfway there and have a crash. This crash represents the disease state. Something has happened to disrupt your journey and you don’t arrive at work, the cell (your car) is broken. Research serves to investigate how this accident happened and find ways of preventing the accident and thus preventing disease. A common approach is to study the crash scene (broken cell) and work backwards to find the cause. Calebs suggestion was to start at the beginning of the journey and map all the events up to the accident to get a clearer picture of what went wrong and identify actions in the build-up which attributed to the crash. By identifying what can go wrong before the crash we can develop treatments which focus on early disease progression rather than fixing the broken scene after it has happened. For example, you hit a pot-hole at the beginning of your journey (not uncommon on todays roads!). You feel a slight bump but nothing to concern you, you are used to hitting pot-holes on that road so think nothing of it. That small bump causes a slow puncture but you continue your journey not knowing this. Some miles later your tyre is flat, you brake but the puncture causes the car to veer off the road – CRASH! In biological terms, you cell is broken, disease ensues and all because of that pot-hole some miles earlier. You could replace the tyre and carry on, this would be akin to taking a drug which replaces the broken function of the cell, but how may times in your life will you need to do this, the treatment is ongoing and eventually you wont be able to replace the tyre again (drug resistance/tolerability). Or, you could fill the pot-hole. Fill it once, fix the problem long term.
Back to biology. To identify the pothole you need to see the whole journey’s events. Biologically speaking you need to see all the stages of the cells life and what is happening at each stage (which genes are active). Single cell sequencing can give you the gene expression status of all cells in a sample (a maintenance report on every car at every stage of the journey). If you order the cells from those at the start of development to those at the end of their life and compare the gene expression profiles you can see the genes of interest at every stage of their journey. Look at which specific genes are active around the time the car hits the pothole and you have a gene/event as a therapeutic target. Sounds simple now! A great analogy Caleb, thanks for sharing.
Special thanks to the team at ELRIG for a great event over the past 2 days and the sponsoring companies who’s contribution allows delegates to attend for free. We look forward to meeting you again at future events