 Well, thank you Victoria for the introduction and welcome to the last talk of tonight So you heard already a few facts about the brain and it might have given you an idea how complex this organ is in our body So with a spinal cord it actually controls or all our movements It defines who we are how we are thinking and when we think about cell types You already heard that they are the neurons and they are actually doing the functional job So they can receive information they can process it Electrical signal and they can pass on this information again to other neurons But neurons are not the only cell types as you might heard of from the last question So for a long time we thought that for a healthy brain for not diseases We thought that the neurons are the most important cell types, but this is not true There are many other different cell types that we now know that they are very important that we have a healthy and functional brain and Today I will talk about the immune system many of you might be surprised that we actually have a special immune system in the brain and It is executed by these little cells that we call microgea But before I go into more detail of this special part of the immune system I will give you an overview of our general immune system So it is divided into two parts There is the innate immune system that we already have when we are born It is very unspecific and it is performed by the innate immune system cells We're also our microglia are part of and then we have the adaptive immune system And this is very specific to patochins So for example to viruses to bacteria but also to some fungi and it is performed by specific cells which are our white blood cells and Why does our brain now have its own immune system because we have for the rest of the body We already have a immune system. Why does it need a special one? And this is because the brain is physically disconnected from our rest of the body So when we take a closer look at the brain We see that blood vessels are also growing to the brain so they could supply their immune system But when we take an even closer look we see that every blood vessel is surrounded by special cells So they are blocking the immune system or the blood cells from the body to the brain which we call this blood brain barrier and There are some restrictions like who gets in the club and who does not so there are stuff that can get into our Brain through this barrier So for example oxygen but also CO2 can get in but also nutrients like sugar and hormones can pass into our brain but also some Toxins like ethanol which some of you might have now taken up in the brain Can also pass into the in the brain But the main reason why we have this barrier is to keep out infections So for example pathogens like bacteria and viruses they are not able to pass into a brain and this is the reason why our brain is very protected and Even though the peripheral blood cells so from our bloodstream they could help with Infections in the brain, but they are also blocked and this is why we need our special immune system in the brain and These cells are the microglia as I already told you They have very small cell bodies and they have very long and branching processes and with this processes They can like sense their Environment they can see if there are any pathogens if there are any changes and when there are proteins or dead cells accumulating in the brain they are They are taking up the trash So they have a process which is called phagocytosis So they can surround dead cells with their processes. They then take them up and then they just take out the trash But when there are now some infections these resting microglia they get into an activated status So they retract their processes and they get in a more bigger rounded shape And they can release than proteins that also attract other immune cells like the T cells And then they can also eliminate these pathogens from our brain also again with the phagocytosis process But what is when this balance system of the immune system in the brain gets in a disbalance? And this is when for example this phagocytosis So taking up proteins or dead cells is impaired or that we have a chronic release of this inflammatory signals Then we get a very like a disease state and then also neurons can be affected and they die And this is the case in fact Alzheimer's disease Parkinson and also multiple sclerosis So all in these diseases the neurons are dying and What I'm now looking in in my project in my PhD is how we can find this neuron and microglia Interaction so we think that maybe the loss of the neurons is just a side effect that the microglia are maybe the disease causing Cell types, so how can we do this in the lab? So we could take some brains, but we already know that there are better options So we tried to make this brain organoid as we have already heard and I hope I'm not going to prison for working with them and then we also need this microglia so the immune cells and We know that in the human development the brain is developing in an area Which will turn out into a head, but I told you that the microglia are immune cells So that they are coming from a different field They are developing from the seolxac Where all our blood cells are coming from and during development these microglia then need to migrate from the seolxac to the brain To the neurons and they're protect the neurons from any infections And so what we would like to do in the lab is to take both parts So the brain and the microglia and put them together in a dish and You already heard about the cool pluripotent stem cells So that's also what I'm working with so we take the skin cells cultivate them in a dish And we add this pluripotency Effectors which you already heard is they reprogramming and then we have these stem cells that are pluripotent Which means that they can develop in different cell types and in my case So I work with microglia which are part the blood cells and I work with neurons So we take now these pluripotent stem cells. Here is how they look in a dish They are growing in small colonies and to generate then the organoids. We dissociate them into single cells And these single cells Aggregate into balls which we call the embryo bodies because they are assembling a stage of embryonic development And then we can put them in a sort of jelly like a hydrogel and they can grow bigger And then you see that they are already like a few millimeters in diameter So now we also need the microglia so the blood cells and therefore we take again the stem cells But we push them in a more blood Lineage so we generate this hematopoietic progenitors, which means they are early stages of blood cells and from these cells We can then generate this microglia and as you can see also in our lab They really like to form these long branching processes. So they look for us very healthy And when we then put those two types together We see Mike Tien read the the microglia that they are actually Able to migrate into the organoid. So they are also doing the same in our lab as they are doing in the embryonic development So now that we have our model system What what can we do with it and I told you that we are Looking at neurodegenerative diseases. So Diseases where the neurons are dying and I will give you an example about Alzheimer's disease because it is the most common neurodegenerative disease and the usual onset of disease in is in later age, so over 65 But the problem is that this disease is is Irreversible so there is no cure you can only treat with Treat the symptoms and to try to slow down the disease progression, but at the moment there is no cure The symptoms of the patients are in general dementia. So the people Forget very easily Like things that they should remember. They also don't recognize their family or friends And in the end they also have very strong difficulties just to perform daily tasks And when we look at the brain we see compared to a healthy brain that the Brain of an Alzheimer's patient is much smaller and it just looks like shrinking and This is because neurons are dying and these neurons are dying in specific region that are also necessary for the memory and For Alzheimer's disease they have been shown to be different causes So on the one side it can be genetically, but these are only one to five percent of the patients Then they also can accumulate certain proteins in the brain that then disturb the normal function there are also risk factors like normal aging or brain injury and Since a few years now The neuroscientists are also looking at other cell types that are the microglia and This could mean that also infections and the chronic inflammation could least lead to the severe diseases So when we take a look at this microglia now an Alzheimer's brain We see that in early stages this microglia have very long processes. So they are still have a Healthy morphology, but in the late stage of of Alzheimer's then they get these round shapes Which means they are activated. They are reacting to some infection or some Problems in the brain and they cannot really function anymore But however, so until now there's not a like a cure or Specific answer why this microglia look like this? So there are still a lot of questions how the microglia are Reacting to the protein aggregates and how this in the end leads to the death of the neurons So now that we have our system we could actually look this more into detail in our lab and we can take Patient samples and to compare it to to healthy individuals and first we can look at genetic risk variants So we can see if there are specific Genetic factors that are causing specific diseases But we can also look now at newer inflammation because we can now also look at the immune system of the brain And we can also test environmental factors or toxins which effect they might have on the diseases and In hopefully in the future. We could also test new therapeutic drugs And I hope that I could show you today with my talk that we don't know Like we have a lot of questions open and that we should not only look at the neurons But also at the immune system and that a healthy immune system also means that we have a healthy brain Thank you Thank you, Hannah. Let's see what kind of questions people have and Who is ready to ask a question? I think there is one on the back very back Just wait a second Hi, thanks a lot for the presentation. I just have one short question How to recognize a neural inflammation? What kind of symptoms are there? Sorry, could you speak up a little bit? Okay, thanks a lot for the presentation. I just have a very simple question. So how to recognize Neural inflammation like what symptoms does it have? So the question was how we can recognize the information So I told you that the microglia can actually have different shapes So this is one that we look at the morphology, but we can also see which proteins are they releasing So they are sending out signals that are signaling in a there is an inflammation. We need to react So they are also trying to communicate this inflammation to other cells to react And there is a question just next to this previous question Thank you for the talk. I have a question. So you said if the microglia has been activated by let's say a better for example Is it possible to block these pathways that activate then did the microglia and maybe then Use it as a therapeutic approach. Yeah So there you can also like activate the microglia But we can also give them signals that they should be more in a healthy way or to block Specific pathway that they need to be this activated. So if we actually know that the microglia are the disease causing Like the disease-causing cell type and that the inflammation is is one of the disease Phenotypes then we could try to block this inflammation So for now, there is no drug or so there are other drugs for Immune or autoimmune Disorders but not at the moment for neurodegenerative diseases Thank you. Is there yes, there is one question here Vicky Oh, there was two questions apparently And so thank you for the talk There is the hypothesis that also depression or other psychiatric disorders are caused by inflammation in the brain And I mean like it seems like a lot of diseases are Alluding back to inflammation and I wonder how this inflammation differs that it leads to so many different Diseases at the end or does it any differ? I don't know So there might be some difference just in the the area of the brain where the inflammation would be so for example in the Hippocampus and the cortex that it is an Alzheimer's that we get like this disease But if we for example look at the the Parkinson's disease where the midbrain is affected So this might be a reason why we get also different diseases Okay, there's was question one more here Thank you interesting talk. How do you make the distinction that a disease is of genetic origin and not caused by external factors, okay? So the Patients are seen by clinicians, which is not my part But when they are getting to the clinic then and they get the diagnosis of for example Alzheimer's disease You can test their DNA So you take a sample of the patient and you can screen for already known mutations That can cause this disease and when you see that there is no change in these genes Then you you assume that is it is not a genetic cause or also if you have Like also other people in your family that also have this disease then you can assume that it is caused by genetic factors Thank you. Thank you. Let's see if there is one more question, which would be last year here in the middle You mentioned at the beginning that the immune system of the brain is separated from the immune system of the rest of the body, so What's the reason for that? So the idea is that the brain is so important when it it does not function properly that our complete body shuts down So it has its own protection with this blood-brain barrier to keep out Viruses or bacteria that cannot infect than the brain Okay. Thank you very much Hanna