 Antibiotics alone don't actually kill the bacteria. They kill most of them, but the immune system is required to finish off the battle and kill the remaining resistant bacteria. So as bacteria are becoming more and more resistant to antibiotics, what we propose to do is to boost the immune response to get rid of these resistant bacterias. The immune system is very complicated, consisting of different types of cells with different specialized functions, and I'm just gonna reduce it down to the essential parts to show you how we want to achieve this. And the immune system can react in different ways with specialized responses, depending on the different threats it can face. And these different threats could be things like bacteria or viruses or parasites. Now these threats also deliver cues to the immune system that show it in which direction it should go, which type of response is appropriate. Well, most of the cells that are reacting are the right type of cells, so the cells that will be able to fight this threat, there's also usually some of the cells from the wrong type of response that are reacting, and these are making the immune response less focused and thereby also less potent. Well, luckily enough, there's not just on signals that drive the immune response, but also off signals that help focus the immune response in the right type of direction. And we want to exploit these off signals to guide everything we have in the immune system towards fighting the bacteria. So what we try to do is exploit these off signals and these are actually delivered through so-called regulatory cells in the immune system. These regulatory cells are capable of just globally shutting down the immune response. However, they can also specialize and only inhibit certain aspects of the immune response. Now, the question of course is, is this specific enough to really just shut down the responses that we don't want to see without hampering the beneficial antibacterial response? We're looking at whether we can really just drive the entire immune response towards fighting bacteria. Well, we believe that we can do this because we were studying a subset of these regulatory cells that was really just shutting off responses against bacteria and viruses, but left all the responses against the parasites completely unhindered. So we have the specificity there and we believe that in other settings, regulatory cells are just as selective and can deliver these selective threats. Now, we need to find out how these regulatory cells do this. If we could identify the switches that they are using to shut down the immune response, we could like in a control room to shut down the unwanted responses, driving everything into fighting bacteria. So shaping the immune response towards fighting what we need to fight. Of course, the question is, what are these switches? And so when we were looking at regulatory cells, the regulatory cells that we were studying, we could see that the entire selectivity could be reduced to one single molecule. So one single messenger, one single switch, that could potentially be targeted therapeutically to really just shut down certain aspects of the response and shape the immune response towards fighting bacteria. Of course, there's still many different types of responses that we're not able to target. So we're now studying regulatory cells in different kinds of settings to be able to identify the switches that these regulatory cells are using in these polarized settings. So settings where only one type of response is elicited, but also only one type of response is inhibited. And we're using nature as our guide here, as pathogens are capable of eliciting these polarized responses. So we have the tools to identify and isolate these regulatory cells in all these different settings so that we can study them in detail. We do this by looking at which genes are active in every single one of these regulatory cells. So by seeing which genes of the entire genome are active in all of these different settings and by comparing them in these different settings, we're able to identify all the genes that they have in common. The ones that are on in every one of these settings, the black ones here, these are the genes that make up the regulatory cells themselves. And we can distinguish them from the ones that are unique, the ones that are only active in one setting, and these are our potential switches. Of course, we still need some time to identify all of these and also verify that they're active and test their potency. We've already seen, just by using one single inhibitor, that we were capable of shaping the immune response towards fighting parasites, away from viruses, away from bacteria, towards parasites. And we believe that if we combine this with additional switches, this effect will only become more strong. And of course, we can also combine this with other approaches to fight bacteria and use this to fight resistant bacteria. As more and more bacteria are becoming resistant to antibiotics, we propose to boost the immune response to really eradicate these resistant bacteria. And we want to boost the immune response by focusing it, by shutting off the unspecific responses. So the responses that are not helpful and focus everything towards fighting the bacteria. Now, if we have all the switches that we can use to turn off the unproductive responses, the ones that are not fighting the bacteria, we have a toolbox at hand that allows us to shape the immune response towards fighting the bacteria. And as the immune system can adapt to its changing environment, bacteria are unlikely to be able to evade the strategy. Overall, we're developing a new approach to focus the immune response towards fighting bacteria. And this can be used in certain settings to replace antibiotic use, but it can also be used in combination with antibiotics or even other strategies to help fight the rising problem of antibiotic resistance.