Designing drugs and making molecules
Dr Bridget Stocker from the Malaghan Institute of Medical Research and Dr Mattie Timmer from Victoria University of Wellington are chemists who design drugs and make molecules. The molecules they make are a copy of the molecules on the cell wall of tuberculosis (TB) bacteria. These molecules are called adjuvants and can be used to improve vaccines against TB.
Identifying TB molecules
Dr Bridget Stocker (Malaghan Institute) and Dr Mattie Timmer (Victoria University of Wellington) are working to identify which specific molecules of the TB bacterium invoke immune response. Once identified, these molecules can be replicated and used to improve the efficacy of vaccines.
Tuberculosis (TB)
Tuberculosis (TB) is a bacterial infection in the lung. It can be active or dormant. If it’s active, the bacteria make people sick and the signs and symptoms of TB are present. If it’s dormant, however, the bacteria are still alive but they’re hibernating. Our immune system is keeping the TB at bay and stopping it multiplying. If a person with dormant TB gets old or their immune system stops working properly, the TB bacteria can become active. The person will get sick and have the symptoms of TB like coughing.
TB is a very old disease and is difficult to get rid of. This is partly because the bacteria hide inside our immune cells and also because the bacteria have a very thick waxy coat that protects them. For this reason, it is hard to kill the bacteria with drugs.
Read this 2015 news article about Victoria University chemists Bridget Stocker and Mattie Timmer's research into tuberculosis.
Treating TB
There are two ways to treat TB. The first way is to prevent the disease through the use of a vaccine. The second way is through medication once you are infected. The problem is that the BCG vaccine we have for TB doesn’t work that well and if you need drugs, you have to take many (perhaps 2–3 different types of drug a day) over a long period of time (approximately 3–9 months). People stop taking the drugs when they start to feel better, but bacteria still remain.
What Bridget and Mattie are doing is developing new drugs as well as looking at how to improve the existing vaccine.
Designing drugs
Bridget and Mattie study TB to see how the bacteria invoke an immune response. They are particularly interested in what molecules are present on its outer surface so they can design drugs that will defeat it. Because TB bacteria have such a thick cell wall, Bridget and Mattie are looking to design a drug that will target the enzymes (or ‘cellular machines’) that build the cell wall. If they can inhibit the growth of the cell wall (through drugs), the bacteria will be weaker and more able to be killed by the immune system.
Enhancing vaccines
Bridget and Mattie are also looking to improve existing vaccines for TB. To do this, they make adjuvants, which they add to vaccines. An adjuvant is a compound that is added to a vaccine to make the vaccine work better. The adjuvant itself will not cure or protect anyone. Using adjuvants to get the immune system going is a bit like putting additives into petrol to get the car engine to work better.
What is an adjuvant?
Dr Mattie Timmer (Victoria University of Wellington) and Dr Bridget Stocker (Malaghan Institute) describe an adjuvant as a substance that is added to a vaccine to make that vaccine more effective. An adjuvant alerts the immune system to the vaccine, making the immune response more immediate and specific to the antigen in the vaccine.
The adjuvant that Bridget and Mattie are making for their TB vaccine is a molecule made from sugars and other products. It is identical to a molecule on the outside of a TB bacterium. Once added to a vaccine, our immune system will recognise this as an antigen or molecule from TB. That will help to kick-start the immune system and allow the TB vaccine to work better.
Making molecules
Bridget and Mattie work with teams of scientists to make molecules. They add compounds together, and these react to form the next molecule. The process is a bit like LEGO, whereby bigger molecules are built ‘brick by brick’ to get the exact molecule required. During this process, Bridget and Mattie need to analyse their molecules using a variety of techniques to ensure that the ‘blocks’ are put together in the correct way.
Making molecules
Dr Bridget Stocker (Malaghan Institute) and Dr Mattie Timmer (Victoria University of Wellington) are chemists who make molecules to replicate those found in bacteria. Making molecules is a bit like cooking. Materials are added and mixed together to make the molecule they are replicating. The compound then needs to be tested to see if it is the one they want.
As the molecules are too small to be seen by eye, one way of analysing the compounds is to use a NMR (nuclear magnetic resonance) machine. The NMR machine records the ‘fingerprint’ of the molecule as a type of graph (or spectra) that they then interpret to determine if the reaction has occurred in the way that they want. To make a TB drug or a TB adjuvant, anywhere from 5–30 individual reactions need to be performed.
NMR machine and spectra
The NMR machine detects molecules in the solution and then produces a graph (or spectra) (see inset), which the scientists then interpret to see if they’ve made the molecules they intended to.
Nature of science
Science is evolving. Scientists are learning all the time and keep working to improve science developed by others before them. The more scientists find out about immune system response, the more knowledge they have to design new drugs and vaccines that will be more efficacious than ones of the past.
