Hi. I'm Phillip, and I'd like to talk to you today about sequencing antibiotics. So before we get into antibiotic sequencing I just want to give you a short discussion of the discovery of antibiotics because it's something I feel like is pretty cool. It's cool because it goes against, probably, what you've learned about science in science class. There are some lessons here that are a little bit different. So, to give you the story, penicillin was discovered in 1928. It was the first antibiotic to be discovered. It was discovered by Alexander Fleming, and he went on vacation. And he was known for keeping a messy lab, and when he comes back after a few weeks. He notices that the cultures of bacteria that he had been studying had been contaminated with a mold called penicillium. And that when this mold had contaminated the bacteria, it had killed the bacteria everywhere that they had contaminated them. And so he said, okay. Well, now we've got something that can kill bacteria. What do we do with it? So this led to a 15 year process from the discovery of the drug to designing the drug and getting it useful so that it would be mass produced for D-Day, 15 years later, when it was able to save thousands of wounded soldier's lives. Antibiotics are so relevant, though, to modern medicine that I think that we have to step back and ask ourselves, would we all even be here. I know that I had something called Scarlet Fever when I was young twice, and that's caused by this bacterium, Streptococcus pyogenes. This is a disease that carried a substantial mortality rate in past centuries. But it's just, you take the antibiotics and you get better now, right? The issue with that is that maybe bacteria is starting to fight back a little bit. We're now starting to see the rise of antibiotic resistant bacteria, such as MRSA or Methicillin-resistant staphylococcus aureus, that resist most antibiotics that are known. And this is troubling. So, for example, here's an antibiotic on a petri dish and the MRSA has spread regardless of the presence of the antibiotic. So let's define what antibiotic really means, and I'm using it loosely to be a substance that goes in and kills bacteria. Where do these come from? Well, they occur naturally, just like the penicillium mold that Alexander Fleming discovered. A mold is a type of fungus, and fungi have evolved over time to have these antibiotics so that they can kill bacteria. They're also produced by other bacteria in order to kill bacteria. One example would be a bacterium called Bacillus Brevis. And that's the bacterium that we're going to study today. It produces an antibiotic known as Tyrocidine B1. So, what is Tyrocidine B1 on a molecular level? It's a “mini protein” called a peptide. So, this peptide is really just a short string of amino acids. There are 20 commonly occurring amino acids. And amino acids are represented either in a single letter alphabet. So, the peptide here is VKLF, etc. Or sometimes, there's a three-letter abbreviation That's shown here. and this amino acid sequence is valine, lysine, leucine, and so on. So we now have a number of questions that we ask about antibiotics now that we know a little bit about them. The first question would be, well they’re peptides, proteins occur everywhere, so what makes these antibiotics special? Second, we would ask, then, how is it that the bacterium produces these antibiotics? And then, thirdly, what the central question is going to be of this lecture, is, how is it that we, as bioinformaticians sequence antibiotics. How is it that we know what the sequence of amino acids in Tyrocidine B1 really is. And so that question is what we're going to talk about today, centrally. Although we're going to discuss these other questions as well, because we're interested in the biology.