Our first Life in the Lab blog introduced the who, what, where, when, and why of MND research. Now, we will take a walk through the early stages of the research journey, from designing experiments to proving the results are ‘true’.
Stage 1: Developing a hypothesis
A hypothesis is a research question that scientists try to find the answer to. Developing a hypothesis is the first stage of creating a research project, and it involves a lot of work! Researchers review what is already known about MND to make predictions about the how’s and the why’s that build upon the incredible amount of knowledge that we already have about the disease. Each MND research hypothesis aims to answer one piece of the MND puzzle, for which we do not yet have answers.
Stage 2: Experimental Recipes
Once a hypothesis has been developed, researchers have to think carefully about how they can find an answer to their research question. This means designing and planning appropriate experiments that will either prove or disprove their theory. We talked about experiments in the previous blog – they are tests carried out, often in a controlled environment like a laboratory, to help researchers learn more about MND.
Importantly, research hypotheses are never going to be answered by a single experiment. Instead, lots of different experiments are needed to provide enough evidence to support, or disprove, the hypothesis. Designing and planning which experiments are needed is so important because it helps to make sure that all the research money is being spent on expanding our knowledge of MND.
Designing each experiment is a bit like preparing to make a cake. Firstly, you need to find a good recipe, or protocol as it’s called in the lab, that you can follow. In the research world, there are often ‘gold standard’ experimental protocols that are published in academic journals, which are a bit like recipe books for researchers. Before choosing a final recipe, you’ll probably need to have a good look through previous recipes and ask yourself: what have others done before that is similar to what I am trying to do? What worked or didn’t work for them? What parts of their work do I need to change to be able to answer my own question? Evaluating the methods and outcomes of previous research is a key step to designing new experiments.
To answer a new research question, it’s all about taking a basic protocol and adapting it to explore something new. In the kitchen, this might mean testing out new flavours combinations, but in the lab, this looks more like changing the type of cells that are used and changing the conditions being tested. Sometimes, to answer new and unsolved questions in research, scientists might need to develop a completely new experiment for their work. This is more like designing a brand-new recipe for a bespoke cake that’s never been made before. Veering into unknown territory can be daunting, but trying new things and taking calculated risks in the lab can lead to important progress in MND research.
Stage 3: Proving a result is ‘true’
As we said above, it takes more than just one experiment to test a hypothesis. MND is an incredibly complex disease, and it is vital that the conclusions we draw from experiments are accurate and trustworthy. This can take more time and resources than you might realise, and is one of the reasons why MND research projects are often funded for between 3 and 5 years at a time.
Importantly, researchers need to make sure that the results of each experiment are trustworthy and haven’t been influenced by anything else. This means experiments need to be repeated, usually a minimum of three times, to make sure the same result is seen every time. This helps to account for technical variation, such as tiny differences in the amount of each ingredient used. Experiments also have to be repeated to account for biological differences between samples. No two biological samples will have the exact same genetic make-up, and this can change the result of an experiment when using different samples. In the lab, differences can come from using cells from different people with MND, or from different mice that have gene changes linked to MND. By repeating an experiment using multiple different biological samples, and then taking an ‘average’ across all the results, researchers can be sure that any differences they are seeing are due to MND and not just due to biological variation between samples.
As well as repeating the experiment multiple times to account for technical error and biological differences, experiments should then be repeated in different models of MND. We talked about models in the previous blog – they mimic different aspects of MND in the lab. MND is complex, and no single model can truly represent MND in a person. While each individual model is useful and can help researchers discover a lot about MND, a result becomes much more trustworthy if it is seen in multiple different models. This is because it becomes more likely that the result is truly due to MND and not just something related to one particular way of modelling MND. For example, a process may be affected in MND cells grown in a dish, but not in a mouse model of MND. This could suggest that other factors are at play, for example, the cells act differently because they are being grown in the dish and are not in their natural environment. The more models that a result is seen in, the more likely it is that the result will then be seen in people with MND too.
So once you’ve proved your hypothesis in multiple experiments and models in the lab, where does the research road go next? Click the button below to continue the research journey towards finding effective treatments for MND.
