Wednesday, 5 March 2014

Designer Drugs: Our Night At The Museum

On Wednesday, we ran a workshop at the London Science Museum, for the "Bio-revolution" Lates session. We wanted to introduce people to the ideas of investigating protein structure and using it to design drugs to treat cancer. 

As it's a Lates session, most people have got a beer or a glass of wine in hand, making for a very relaxed and entertaining evening! It was a fantastic chance to showcase our new 3D printed protein structures and drugs, and they went down a treat. It was such an invigorating experience; so many people asking questions and getting involved. It was also the most popular Lates session to date - nearly 7000 people showed up!! 

Although it was an incredible amount of fun, I was absolutely gutted that I didn't get the chance to go off and explore the rest of the museum myself. There was so much going on, and so many researchers there ready to get the public involved in their science. 

As for our session, it started with an animated video made by the very talented Jeroen Claus, explaining how some cancers develop and one of the ways in which researchers attempt to target it. You can watch the video here




After that, people got a chance to play with the 3D proteins themselves. We had big 3D printed HER2 proteins, with 3D printed flexible drugs that (may) fit into the ATP pocket (or binding site). We started by observing that while ATP fits, it falls out pretty easily when you tip the protein upside down. It was just a nice way of visualising the fact that ATP binds loosely, and a drug just needs to fit more tightly in order to compete with it. 

Enter our drugs (from the top of the fingers down to the palm): Staurosporine, ATP (for comparison), Lapatinib and Taxol.




Staurosporine fits really well - in fact, it fits too well. It fits so well that it likes to bind to loads of ATP pockets - not just the ones in HER2. The fact that it's so promiscuous means that a lot of messages that we need to be transmitted are blocked along with the HER2 ones, meaning that our cells die. So it's used in the lab, but is rubbish in the clinic. 

Taxol is massive. It's actually a natural molecule that was isolated from the Yew tree, and it took forever to recreate in the chemistry lab because of its unusual structure. That unusual bulky structure also makes it a poor fit for the ATP pocket. You can shove it in if you try (and believe me, some of our visitors definitely tried) but you get the idea that it wouldn't happen in the body naturally. Taxol is used to treat cancer though, as a chemotherapy agent. It targets the cytoskeleton (check out my last post for more info on that), stabilising the cell structure and preventing cell division. 

And finally, lapatinib: our winner. I think it looks like a longer ATP - and a lot of drugs that target these sorts of proteins are modelled on the structure of ATP, because we know that fits. It extends further into the back of the pocket, and will be interacting with the amino acids inside. Lapatinib is used as a secondary treatment for HER2-positive breast cancer in the US. 




This sort of personalised medicine isn't going to solve everything - drug resistance is still a big problem. But it does offer a more specific treatment with fewer side effects that chemotherapy. You can read more about targeted cancer therapies in far greater detail here

Overall, we had a lot of fun! 3D printed proteins were a great way to explain structure and drug development, and hopefully we'll get to use them a lot more in the future. 

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