 When you're sick or someone you care about gets ill, you hope that there's a drug that will make everything better. Sometimes it's a quick fix like taking an aspirin for a headache, but what happens when it's not a quick fix? Do you ever wonder where drugs come from? If you close your eyes and try to picture a drug factory turning out compounds to keep us healthy, what do you see? Some of you might picture a scientist in a lab, but our best bet for finding new drugs is not a scientist, it's nature. And so today I'm going to tell you how my lab is using clues from nature to identify new compounds for treating cancer. The animals, such like snakes, gila monsters, centipedes, and even snails are probably not what you pictured in your drug factory, but some of these venomous creatures have produced blockbuster drugs to treat diabetes, hypertension, and chronic pain. In their interactions, the predator-prey interactions of these venomous animals, they've produced compounds that have evolved over time that are efficient, fast-acting, and specific. As you'll see here in the video, that snail is being specific, very fast-acting, and efficient in eating that fish. And so how is that possible that a slow-moving snail could eat something as fast as a fish? The answer is the fish never had a chance. This snail has a venom, which I like to describe, kind of like a cluster bomb. It's not one peptide, but it's several peptides that have evolved over time to basically shut down the function of that fish, and these are peptides that have evolved to hit their specific targets. And these snails can produce several of these peptides, each of which are very good at manipulating signals. And so if we think of diseases as disorders for which the signals can be turned on or off, then cancer cells have the on signal on to divide all the time, which leads to excessive proliferation. And so if we think of venom peptides as ways of manipulating or shutting down the signals in malfunctioning cells the same way they shut down the system of the fish. And how do we find these peptides? So traditional methods are based on size and quantity, and it's because those methods required big and bountiful specimens. In my lab, we're using evolution and diversity to help us to do more target-driven discovery of the species that are important for drug development. So I like to describe venomics as sort of this marriage between evolution and technology. By investigating the venom of these predatory animals combined with modern-day techniques like RNA and DNA sequencing, we've sort of propelled the discovery of novel compounds that can be used in drug development. And so we start by building this sort of family tree of snails in which we are able to describe how one snail is related to each other. In doing this, we quickly identify the species that are actively using venom, the ones shown in black, from the ones that don't. This crucial step saves us time, money, and efficiency, and it helps us to more quickly identify the compounds, which might be giving us different signals. And so we did this to find T. enelis, the snail that you see here. We focused on this snail because it's in a different clade that has not previously been characterized. So when we were looking for peptides that might target cancer, we wanted to find things that were previously uncharacterized but also will give us those strong peptides for shutting down signals. And this is what we found. This is the structure every biologist in the audience will recognize as the structure of a peptide. This is the TV1 peptide. It has 21 amino acids, three disulfide bonds, which are highlighted there in color, and it's a very unique structure. And this unique structure of TV1 made us think perhaps we can find a molecule that's doing something different. And indeed TV1 does. TV1 is killing cancer cells and it's doing it at a rate higher than normal cells. This is truly important because all of the drugs currently on the market, they cannot discriminate between normal and cancer cells until they kill them both at the same rate. So with TV1, we think we possibly might have a compound for which we can treat cancer cells with reducing the risk to healthy cells. And so we analyzed TV1 using several biological acids and we found that it not only kills cancer cells, but it specifically is turning off liver cancer cells. And so in the lab, we're now trying to figure out what is the switch that TV1 peptide is turning off in liver cancer cells, similar to what it would have done in the fish. So to give you a summary of what we've done so far, we use nature to sort of learn the lesson of which of these snails are producing venomous peptides that are manipulating signals in cells. We investigate the venomous compounds, various ones, and we try to identify the peptides for which there is a biological assay that targets cancer cells. And so I've given you just one story of how we're learning from nature in my lab. But there's lots of work to be done before we convert TV1 into an actual drug. But this strategy, this venomic strategy that we're using, we know that it works and we know that the peptides that we're finding will manipulate cells. So nature has the answers. We just have to trust in what I like to call the killer snails. Thank you very much. Thank you.