Drug discovery 3.0: more effective and humane
Discovering effective new drugs is a long, expensive and uncertain process. Laura Heitman wants to improve this by finding out more about how drugs bind to proteins that play a role in disease. She calls it ‘drug discovery 3.0’. Inaugural lecture on 9 December.
The hunt for new candidate drugs takes money and time, and the results are very uncertain. Because drugs that first appear to be promising, often end up not working well in the human body. With her research into molecules and targets, Laura Heitman hopes to help discover drugs that will end up on the market.
Riding an elephant
Many drugs are small molecules that influence proteins that play a role in disease. This can mean activating or inhibiting this protein. The drug ‘steers’ the protein. To do so, the drug must first have a target on the protein in question. To explain this process, Laura Heitman will compare it in her inaugural lecture with a child (the drug molecule) that jumps on the back of an elephant (the protein) to ride the elephant. Heitman’s research is into new target proteins: would you be able to steer the elephant if you grabbed its tail or trunk? She also looks at the speed at which molecules bind to and release from proteins because this determines how effective a molecule is at influencing its target.
‘I think that in five to ten years we will start to see drugs in clinical trials that are based on this research.’
Expand repertoire
For her research Heitman is looking at a dozen proteins within the family of membrane proteins. This is a specific family of proteins on which 35% of the drugs that you can buy at a pharmacy act. ‘Whether my research is applicable to other proteins within this family of membrane proteins remains to be seen. Conceptually it should be because each protein has a target. So I would venture to say that all that I am learning now about types and rates of binding is applicable to all 800 membrane proteins, and possibly beyond. I firmly believe that this is going to help our search for drugs, and I think that in five to ten years, we will start to see drugs in clinical trials that were developed based on this research. So I call it drug discovery 3.0: this knowledge will greatly expand our repertoire within drug development.’
‘I love to see when a molecule that I developed works as it was supposed to.’
Credit due
But with ‘drug discovery 3.0’, Heitman means more than just expanding the methodology. Research must also be ‘collaborative and humane’, she says. By ‘collaborative’, she means that drug discovery is a team effort, whereas in academia success is still often measured by individual results. She calls for shared authorship so that all team members get the credit they deserve. Heitman is also involved in multidisciplinary drug discovery and development, and founded the LED3 virtual institute with several institutes in Leiden (in biology and chemistry). LED3 stands for Leiden Early Drug Discovery and Development. Thanks to its internal interdisciplinary knowledge and collaboration with the LUMC and Leiden Bio Science Park, among others, LED3 hopes to find new concepts for drug development. ‘My research is fundamental. I don’t look at how the molecules we develop behave in living organisms. But that would be possible within LED3. And I think it’s great to see when a molecule I’ve developed works as it’s supposed to.’
Rat race
By ‘humane’, Heitman means fighting the rat race that academia has sometimes become, where there is little room for free time and burnout is sometimes seen as a normal part of an academic career. How does she plan to achieve this ‘humane’ research? 'First and foremost, I obviously hope that it is clear within my own research group that while we work hard, there is also room for free time. However, I can see that there is still a long way to go, even within my institute. Different department heads have different views on the subject. I think there should be room for other things in life besides research. But I only found this out after I burned out myself. So I understand that people within academia have different views. It is important to speak out against it anyway: you can do cutting-edge research without it taking over your whole life.’
Text: Jan Joost Aten