The human brain is home to billions of cells, each playing an essential role in our ability to think, feel and move. But what needs to happen within these cells to send signals throughout the body?
During a recent public lecture, Van Andel Institute’s Dr. Melissa Hoyer, assistant professor in the Department of Neurodegenerative Science, gave attendees a look into the incredible processes that make our cells tick and impact overall health.
Watch the lecture below:
Photo caption: Dr. Melissa Hoyer, left, speaks during Van Andel Institute’s Public Lecture Series.
Video transcript
Note: The following transcript has been edited for readability. Click a timestamp to jump to that part of the video.
Maranda [0:02]:
Good afternoon and welcome to the 2025 Van Andel Institute Public Lecture Series. I’m Maranda from WOOD TV8, and it’s exciting to be here to kick off this illuminating event, one that will give you an inside look into the groundbreaking research underway right here at the Van Andel Institute. Today, we are taking a look at the building blocks of brain cells. The brain is made up of millions of cells, each one playing an important role in our everyday lives. But what exactly goes on inside these cells? What makes them tick? Well, that’s what we’re here to learn today, and we have the perfect scientist to guide us through the conversation: Dr. Melissa Hoyer. Dr. Hoyer studies the fundamental cellular process that supports brain health. To date, her research has revealed important insights into several critical cellular systems required for normal function and detailed how errors in these vital processes contribute to disease. Today she’ll, guide us through a behind-the-scenes look at how our brain cells work, how they contribute to health, and when things go awry, how they influence disease. Once the presentation is done, we’ll have time for a Q&A. And if you are joining us virtually, we ask that you use the chat room to post your questions. At this time, please join me in welcoming Dr. Hoyer.
Dr. Melissa Hoyer [1:35]:
Okay, thank you Maranda, and thank you all for coming. I’m really excited to tell you today about the building blocks of brain cells. So, today we’re gonna be covering a lot of different things, but first we’re going to just understand what these cells are, these cells that make up the brain called neurons. And we’re gonna really explore the inner workings of these cells, these brain cells called neurons. And then we’re going to understand what, how these are actually built and what are the little parts of the neuron that are helping these different functions. And then we’re gonna talk about what happens when things go wrong and how this leads to different neurodegenerative diseases. And so, let’s just look broadly at the nervous system. So, what exactly is the nervous system? Well, this is the system throughout your body that helps you think, move, have emotion and sense different things when you touch them.
And so, you have here a network of different neurons that are going to be signaling back and forth between the brain in order to move, think, sense and have emotions. So, these are kind of the things that we think about doing. Extending your arm and such is a movement, but the nervous system also regulates things like breathing, your heart rate and your body temperature as well. So, how exactly do we perform all these functions? And how does the nervous system help us do this? Well, as I’ve alluded to, this nervous system is full of many different parts called cells or neurons. And these neurons can communicate with one another. So, you have a nerve, a special type of neuron, out in your hand that is sensing a touch. It’s communicating back to the brain. Say you’re touching something hot or cold, and it’s telling you to remove that.
So, there’s this communication constantly between your brain and your different parts of your body. And this is all facilitated by the cells called neurons. So, then, what happens in neurodegenerative disease? Well, we start to lose these different functions. So, for example, in Parkinson’s disease, one of the first things we see is lack of control of motor function. And then eventually you also lose things like cognition. And each of these different diseases loses different parts of these nervous system functions. And why exactly is that, though? Well, simply put, what’s happening is that the neurons in these different locations are either defective or completely lost in different parts of the body. And so, in the case of Parkinson’s disease, the neurons in your brain that are regulating these neuro — these motor functions are now either defective or completely lost.
So, if you take the whole system of the nervous system in the brain, you have about 86 billion different neurons. So, what are neurons that keep using this word? They are simply just a specialized type of cell. So first we’re gonna look exactly at how these work. And then we’re going to look into the building blocks inside of these. So how does this tiny little neuron that I’m showing you here communicate these signals so quickly throughout the body? Well, they link up to one another. And so, the signal can go from one neuron to another, and it can propagate. So, this is called signal propagation. One neuron senses the signal and then it moves it to another neuron. So, but if you look in a field of neurons, there are several different neurons in just this image alone that I’m showing you here in green. And then think of the three-dimensionality of your brain and your nervous system and how many different neurons that really is. And they’re forming all these contacts, and they can signal to one another very quickly. So, as an analogy, you can think of this somewhat like the internet, where you quickly get a signal going from one part or one country to another over time. So, you can do this very quickly by having all these different connections.
But now we’re gonna talk about specifically how neurons do this. How does a neuron sense a signal and then propagate it or move it to another neuron? Well, these cells, these specialized brain cells called neurons, have different parts. They have the cell body, they have these dendrite areas and axons. So simply put, you have a, a neuron that first has a signal, and then it’s going to need to move it to another neuron. So, you have a presynaptic neuron and a postsynaptic neuron. And together these are gonna form these tight connections called the synapse. And this is specifically between the axon of one neuron and the dendrite of another. So, the synapse is just this part in between the two neurons where the signal is going to be communicated. Now, let’s zoom specifically into that synaptic region. So, this is called a synapse, or a synaptic gap.
So, before we’re looking just at this circular area where the two neurons are contacting, and now we’re really zooming into that area. So, on the left, I’m showing you the presynaptic neuron and that axon, this is where the signal is first gonna be at, and then it needs to be communicated to the post-synaptic neuron and the dendrite. So, what is required for this? Well, the axon has these little bags of things called neurotransmitters. And these neurotransmitters are the signals to further propagate. So, the impulse comes into the axon of the presynaptic neuron, and this tells these little bags of neurotransmitters, these signals, to be released. These small neurotransmitters will then go and bind the dendrite of a neuron that is contacting at the synaptic gap. And then this will have the response keep going. So, this is how neurons communicate through these synaptic gaps.
What I wanted to now show you, though, is what this looks like in a lab. How can we study these, these signals between different neurons? So, in the lab setting and in a research setting, we can take neurons from different model organisms. So, we can’t really take neurons from a human brain. But we can take neurons out of mice and rats, and we can even study neurons in fish and in worms. And we can see these signals happening. Specifically in my lab, I use induced pluripotent stem cells. So, these are human cells, though. So, you can take a human cell from say, a fibroblast or a skin cell, and you can then generate these stem-like cells. So, from a cell that’s already one type, like a skin cell, you can go back to something called a stem cell. So, a stem cell just means it’s a certain type of cell that can go to any other type of cell type.
So, at that point, we take the stem cell, and we can generate human neurons from that. So, and again, in my lab, we use these neurons. You can take neurons — you can take tissues from patients and create stem cells and then generate neurons, or you can just take a normal human and that has no sort of disease, and you can make stem cells and convert them to neurons. So, this is my lab. I just started here at the Van Andel Research Institute in July. So, I have a small group, but I will say they’re very mighty. I have a technician, Katie Colesa, Ahlam Soliman, a postdoc, and then Kashfia Neherin, a lab manager. And what we love to do is study these different neurons created and generated from stem cells under a microscope. And so here, Kashfia is looking at stem cells from humans that are beginning to differentiate to neurons.
So, you can already begin to see those large circular regions, which are the cell body that I mentioned. And then you have these longer regions, which are forming those axons and dendrites. And these are gonna begin to form those connections, those synapses. So, we want to let these mature for long enough that we get a lot of connections. So, this is 20 to 30 days later. So, our experiments, they take a long time, but what we can see is actually the signaling between the different neurons. So, the cell bodies now here are more grouped together, and then you see those long areas — those are those long axons reaching very long distances. So, in, say, your actual body, some of these long axons can be up to a meter and you could have these signals going all the way from your brain to different parts. But now in a dish, we’re contained, and we can look at these little signals between each other.
So, I’m showing you here a light microscope image. But in order to see these signals between neurons, we actually use something called the fluorescence microscope. So, we have a sensor that will show the triggering of neurons in it — and — using fluorescence. And so, this is just a bigger microscope and here is what it looks like. I used to work on the microscope a lot during my postdoc before I came here to the Van Andel. And so, I spent many hours just looking in at these dishes, at neurons. And right now, the light is on. But I will say in order to do these fluorescence microscopy experiments, you actually have to turn the lights off and hang out in a dark room for somewhere between one to five hours sometimes. So, it seems hard ’cause you’re alone in this dark room, but what you see under the microscope is simply amazing.
You get to see these neurons firing over time and it’s really captivating how beautiful these networks can be. Okay, so, we know that neurons can fire, they can send signals from one to another, but how exactly do you communicate? So, you need a lot of basic neuronal functions. In order to form these synapses and to communicate from neuron to neuron, you need to be able to make these signals that are going to go from one place to another. You have to make those neurotransmitters. You have to get those materials out at the correct destination out at that, at that post, or that, presynaptic axon. You have to, after the signal has happened, you have to be able to degrade these signals. And, at times, these signals can actually become damaged. And parts of these at the synaptic at the synapse can become damaged and you need to be able to remove those.
And then you have to be able to time this release appropriately. And all of this requires a lot of energy in your brain. So, for this actually to occur, you need a lot of energy. And in the context of disease several neurodegenerative diseases, which include things like Parkinson’s disease, Alzheimer’s disease, and ALS, what’s happening is that these basic neuronal functions are disrupted. So, you have neurons that are degenerating, you have neurodegeneration. The signals are no longer being able to be triggered for this communication to happen between the neurons. And then the materials are not actually getting to the right destination. Things are not properly being degraded. So, you have a buildup of a lot of components at that site. And then finally, you’re no longer having the energy that you need in order to perform this signal propagation.
Okay, so, what really makes the neuron work? Well, we have to think about what makes every cell in your body work. And that includes these tiny parts of each cell called an organelle. So maybe you’ve heard of something called the nucleus, the endoplasmic reticulum — that’s always a fun one to say — mitochondria, lysosomes. So, what are all these organelles doing and what does this have to do with neurons signaling from one to another? Well, let’s take a step back and think of each cell as if it’s a city. What exactly do you need to make a city like Grand Rapids work? Well, you need a place where you have all your records at. You need a city hall that will have all the really the plans for the city. And then you need to have factories where you’re building and making all the materials to keep building houses, to keep building the businesses that you need.
You also need an energy source. You need these power plants because people need to be able to turn their lights on in their homes. You also have to have a place to put all of the materials that you no longer need. So, you need a place for all of your garbage to go and for hopefully some of this garbage to be recycled. And then you also have to have these complex roadways going from every single place so that you can keep doing these functions. And so, in the cell, here are organelles that are performing these functions for every type of cell, including in a neuronal cell or a neuron. So, the city hall the nucleus is somewhat like the city hall. It contains all the plans that you need for each cell in your body, including your neurons.
And then the endoplasmic reticulum is like the factory. It’s going to be building all the materials that the cell is going to need to function. Mitochondria, a lot of people know the mitochondria as the powerhouse of the cell. Well, this is like the power plants of the city. Lysosomes are really those degradation centers, and they’re also needed to recycle new materials out to keep building at the factories. And then you have these different complex roadways throughout the city. And these are the microtubules. So maybe you have seen something like this back in your seventh-grade biology where you have a representation of an animal cell with organelles and that maybe at one time, you had to memorize the function of every single one of these organelles. But a lot of us only remember probably making some sort of model of a cell, potentially making a Jell-O mold of this, and adding in different pieces of candy to represent things like the endoplasmic reticulum or the mitochondria.
There’s even a YouTube video that you can go through, where you can make a cake and then decorate it like an animal cell. One person even took a cantaloupe and designed this. So really, this is just emphasizing that you have all these different organelles. But what I want to show you today is that these models are really barely skimming the surface of what’s happening inside actual cells and, specifically, inside neurons. And I really want to emphasize how intricate a place it really is inside a neuron. And so we’re gonna go back to that fluorescence microscope. And in here we were looking at an organelle called the endoplasmic reticulum, which is represented by Twizzlers, this is what the endoplasmic reticulum actually looks like when you look on a fluorescence microscope at just a normal animal cell. So it’s very much, strikingly, not Twizzlers.
It is a network of tubules that are dynamically ranging over time. And what I wanna emphasize here is that these factories that are the endoplasmic reticulum are actually spread throughout the entirety of the cell, ’cause you need materials at every part of the cell. So then, what does this look like in a neuronal cell? Well, this is fluorescence microscopy of the endoplasmic reticulum in a neuron. So, these are these factories again, and I just wanna emphasize that these are spread throughout the entirety of this cell body that we were talking about, throughout those axons and throughout those dendrites. Here’s another representation, another image of the endoplasmic reticulum again, in a neuron. And again, you can really see that it’s in the cell body, but it’s going all the way throughout the axons and the dendrites. So why do we need this endoplasmic reticulum factory there?
Well, let’s keep zooming in even further and really looking at things like the cell body, the dendrite and the, and the axon. In order to do this, we need an even bigger microscope. We need something called an electron microscope so we can get better resolution, so we can see things better. But we can only look at small regions of a neuron with this. So first we’re just gonna look in there at that cell body. And what you can see is that the endoplasmic reticulum, the factory is now represented in yellow here, these mitochondria, which are these factor-, these power plants are intertwined there with the factories. So, we got the power plants, we got the factories, they’re all intertwined, and they’re all functioning together in this intricate part of the neuron called the cell body. We can also look out here at these dendrites, which are the areas of the neurons that receive signals.
And again, we see the endoplasmic reticulum there and mitochondria there. So, the cell boundary here is going to be represented in cyan, and then the endoplasmic reticulum is again in yellow, and the mitochondria are in green. It’s gonna remove the cell boundary, and what you can see here is again, this beautiful intricacy. So out here where we’re receiving the signals, we have again, these factories that are needed and the energy needed right there. Let’s look out at the axon. Now, in addition to showing you these factories now, and these power plants — the endoplasmic reticulum and the mitochondria — I’m also showing you these small blue structures. And this, again, is the axon. So, the axon is where those neurotransmitter-filled bags are at, and those are represented here in blue. So right here, where we’re gonna have this signal going from this axon to a dendrite of a potential other neuron adjacent to it, we have these just completely the axons have just completely loaded with these neurotransmitter-filled bags.
And to make these bags, we again need materials which are coming from that endoplasmic reticulum. And then we also have energy because we need to be able to release these at the right time. And that energy is being supplied by the power plants, the mitochondria. Okay, so all of this is again, just to show that cells, animal cells, neurons, they’re all very intricate places, and we need the functions of these organelles in order to help them work. We need to have the organelles spread throughout the entirety of each of these cells, including these neurons, which are very long. And today I talked to you a little bit about the endoplasmic reticulum and the mitochondria, but I’m also gonna be touching on more about what’s happening with these lysosomes.
But before I do that, before I go more into the details of organelles and why they’re important, I still want to emphasize that everything in the cell is also moving. And this requires these roadways that I was talking about. So, in the city, you have all these different roads. These roads in the cell are called microtubules. So, spreading all the way from the cell body out to the axon are these things called microtubules. And really, it’s just this platform that it is created, that these motor proteins sit on and they walk from place to place on the microtubules. So, organelles can actually be linked to these motor proteins like kinesin and dynein. They’re gonna walk on the road and these are gonna pull mitochondria from one place to another. They can also pull things like the endoplasmic reticulum around as well.
So, going back to our tool here, the fluorescence microscope, we can now look at a network of the endoplasmic reticulum out in the axons and the dendrites and also the mitochondria. But here I’m just gonna focus in on just the mitochondria that are throughout the axons. And so, they’re represented here in white. And then if you sort of look at the middle of the screen here, you can see that over time these are actually moving around and there’s a mitochondria going straight down these different axons. So again, there’s this microtubule road that I’m not showing you here, but the mitochondria is gonna be linked to a motor protein that’s going to be trapping it, trafficking it, trafficking it from place to place.
So, again, each cell is like a city. We have these organelles that are performing these different functions, and they move around so that we can get all these functions happening in each part of the neuronal cell. But what exactly happens in the disease state now? So, again, I will just mention that in these neurodegenerative diseases like Parkinson’s, Alzheimer’s, ALS, you get neurons that are defective. So, you’re not getting signals triggered, you’re not getting materials in the right place, and you’re getting a lot of materials in places that are building up inside the cell. And then they don’t have energy that they need. So, I’m just gonna show you one example of this so that you can begin to understand why a neuronal cell, or a neuron would die. And so, one route to having neurodegeneration and these neurons becoming defective is having these organelles become damaged.
Now, there’s a lot of different ways that neurons can become defective, but this is one example that my lab specifically works on. So, oftentimes, you would have a healthy mitochondria providing the energy that the cell needs right there out in the axon. However, over time some, some damage can actually occur to mitochondria. When this damage occurs, you have a loss of energy, but also, all the little reactions that were happening in the mitochondria to produce this energy actually require pretty toxic products. And so, you get this release of a bunch of toxic byproducts when you have damaged mitochondria. So, not only do we have garbage in the way, but we have pretty toxic garbage there, and we need to be able to handle that. And we gotta get that in the garbage truck. We gotta get it off our curb. We need to get that to the dump.
So, how do we do that? Well, we need, I’m introducing yet one more organelle, and that’s called the autophagosome. And so, the autophagosome is like that garbage truck. It’s going to sense that there’s a damaged mitochondria, it’s going to bind the damaged mitochondria, it’s actually going to grow around it. So, we’re gonna sequester that damaged mitochondria, that toxic garbage, into this autophagosomal structure. And now this autophagosome is going to go and be transported to lysosomes. And so, where this autosome is like the garbage truck, it’s going to move then to the dump, which is the lysosome. And this damaged mitochondria is going to be degraded. Now, they have, the lysosome has everything it needs to degrade this toxic mitochondria. But I will say, the lysosomes are also really important because not only are they degrading that damaged mitochondria, but all the materials that were used to build that mitochondria are going to get recycled back out from that lysosome. So, this is also like a recycling center. All those materials are going to go back to those endoplasmic reticulum factories. So, we can keep building and keep that neuron functioning.
But one thing I want you to appreciate is what happens if you get damaged way out there in the axon. Well, something that’s a little bit peculiar, and what my lab likes to study, is how we can have damage out in these axons and yet get all the way back to where the dump actually is. So, lysosomes actually reside here at the cell body. And so, you have a damaged mitochondria way out at the axon. And so, you need to be able to sequester that into the autophagosome out there. And then these autophagosomes, these garbage trucks, are going to move all the way back to the cell body to get to the dump, to these lysosomes. And this is just a representative image of these autophagosomes, these garbage trucks, which are containing these different materials that need to be degraded, like damaged mitochondria, and you can see them trafficking throughout the axons over time. And again, they’re bringing these damaged organelles and different components that need to be degraded back to the cell body.
Okay, so what specific diseases are really related to this process of not being able to successfully clear damaged organelles? So, I’m just going to take one neurodegenerative disease in particular, and this is Parkinson’s disease. This disease is characterized as a movement disorder, and it worsens over time, and you can also have cognitive decline. So, as I mentioned at the beginning, your nervous system is what regulates your functions like movement. And so, the neurons that are specifically regulating those functions are degenerating. If we take samples from postpartum or, or sorry, from brains from patients that have died, unfortunately, we can look in at the neurons and we can see exactly what is happening to those neurons specifically. And one distinct hallmark of neurodegeneration and Parkinson’s disease is a presence of these things called Lewy bodies. And maybe you’ve heard before, of a protein called alpha-synuclein.
And alpha-synuclein is what is really aggregating there at this Lewy body structure. So, the middle panel here is showing you an example of a neuron that contains a Lewy body, and then on the very left panel there is just showing you more of a graphical representation of the 3D picture of the Lewy body. So, what is the Lewy body? I did mention that it has this clusters of this protein called alpha-synuclein in it, but also with the alpha-synuclein protein, there’s this clustering of organelles there and there’s a lot of different damaged organelles at that place. And, so, it can be thought that these Lewy bodies are really just this large deposit of this trash that’s happening in the cell body. And so, where we’re having this garbage dump at, where all the lysosomes are, you have basically too much trash there and you can no longer have really these functional lysosomes that are degrading everything that you need to keep these neuronal functions going. Because again, these lysosomes are also recycling centers. So not only do you have a bunch of potentially toxic trash at that region of your neuron, but you’re no longer getting the building blocks you need to keep neurons functioning.
And so, Parkinson’s disease is actually a very complex disease to study. There’s a lot of different ways that you can get Parkinson’s disease. Unfortunately, there are familial ties. So potentially your parents, one of them or two of them both have Parkinson’s disease and they, they give you the genes of the disease. And then there’s also these prevalent sporadic cases of Parkinson’s. Some of this is due to your genes and some of this can be driven by different environmental factors including toxins. So really, a lot of what my lab does and a lot of other labs, is really look at these genes that are frequently mutated in Parkinson’s disease patients. So, I’ve listed a few here, like this LRRK2 alpha-synuclein itself, that protein that’s aggregating at that Lewy body has mutations or replications in it. And there’s other things like PRKN and PINK1.
So, what are these genes? These genes are things that are going to create proteins. And proteins are really what creates these other building blocks, these organelles. And so, the proteins are really driving the organelle functions that I was just telling you about. So, specifically, PRKN and PINK1 are very much related to that degradation of damaged mitochondria system that I just described. Things like ATP13A2 are related to lysosomal health, so you make sure you keep getting that recycling happening. And then each of these is somewhat related to different processes that are happening in the cell and different researchers are looking at other avenues of how these certain proteins are functioning in a way in the cell, to either result in neurodegeneration or to be protective.
And so, again, Parkinson’s disease and really all other neurodegenerative diseases are very complex. You have some of this genetic risk and you have environmental risks, and together this is creating a disease state. So, really what my lab tries to do, and many other researchers, is try to understand the various ways that we get these neuronal cells degenerating and getting these neurodegenerative diseases. And insights from this work then can help us try to tailor and generate different therapeutics that specifically target each of these specific pathways that I’ve just been talking to you about. So, we can try to target efficient organelle degradation. So, if organelles are damaged, we can try to have different therapeutics to really drive this degradation of organelles in a better way. That’s just one example of the many different therapies they’re trying to really be studied at this time. And here at the Van Andel Institute, we have a lot of different labs that are focused on unique neurodegenerative diseases and have unique angles in studying these different diseases.
And now, just in summary, I’ll just kind of give you a full picture view of exactly what I’m talking about and how these neurons are functioning. So, the nervous system as a whole, again, is helping you do a lot of different functions. It’s helping you move, it’s helping you think. And at times what happens is that the different neurons that make up these systems are either degenerate, can no longer function, or they completely die. And that means the communications that you need for things like movement no longer can occur. But why exactly do neurons die? Well, I took you inside a neuron to see all the complexity within it, and each neuron is like its own city and a lot of different things then can go wrong. I showed you the example of when one organelle becomes damaged and how you need to clear this damage, but other things can happen in the city like that can result in disease.
So, in short, neurons can die in a lot of different pathways. The city can no longer produce the energy that it needs, so the neurons can no longer fire. There are too many damaged or hazardous materials that form these large Lewy bodies, like in the case of Parkinson’s. The roadways are completely blocked. You can’t even get to the garbage dumps anymore. You can’t get to those lysosomes. And then factories generally shut down if they can’t have those materials that need to be recycled from the lysosomes. And therefore, unfortunately, you get neurodegeneration. And so, some key takeaways from today. First of all, I hope you learned a lot about the nervous system and specifically about neurons and how these communicate from one place to another and how the signals between one neuron to another neuron occurs. And each neuron itself is like a tiny city, and it has a lot of different functions. And each of these functions is very important to study in the terms of looking at it in neurodegenerative disease.
So, in neurodegenerative diseases, again, we have defective neurons. We no longer can get the communication that we need. And then, researchers are studying various aspects of how these communications are lost, if there’s environmental influences, if there’s genetic influences. And there’s a lot more to understand because to be honest, we don’t actually know everything about just the basic cell processes that are happening. So, that’s really what my lab is trying to focus on — is how exactly do we efficiently degrade organelles just in a healthy neuron before we can even begin to imagine how this is becoming deficient in a neurogenic disease state. And with that thank you very much for your attention, and Maranda is gonna come up and ask me some questions.
Maranda [36:16]:
So exciting. If you have a question and you are in person with us, we have friends from Van Andel Institute that will be manning the microphones. If you can raise your hand, wait until that mic comes to you and then ask a question. We have about 400 friends joining us virtually. If you are logged in virtually and you have a question, go ahead and type that question in and we will try to get to as many of those as we can. Thank you so much.
I wanna start off and, based on the work that you are doing, what would you recommend are some of those preventative things we can do? So, we don’t have all that garbage piling up and our roadways are clear, and those factories are functioning. Are there specific things? And I know nothing is definitive, but from what you’ve seen?
Dr. Melissa Hoyer [37:00]:
Yeah, so, in general, just overall good health is very important to making sure these processes are functioning the way they should be. So, we think of taking antioxidants, well, when I was talking about those reactive byproducts that are being released from the mitochondria, that’s like something with antioxidants would help sequester. In terms of what you could specifically do is something you would probably wanna consult more with your doctor, if you’re thinking of changing your diet in any way. But just general health, I think, is helpful. But again, there’s so many complexities to the environmental factors that we don’t even know we’re being exposed to and our genetic risk.
Maranda [37:48]:
Good. Who’d like to start? Right in the middle?
Audience Member [37:54]:
Hi, my name is Nancy. I just wanted to let you know I really loved your picture of the city, and I feel like that could be applied to many more things besides just the brain, you know, whether it’s our liver or our body or, or whatever, even outside. But I’m just wondering, in terms of studying the brain, we talked about, like, after death, wait until people die. Are there any advances being made in terms of how we can study the brain while people are living, whether it’s healthy brains?
Dr. Melissa Hoyer [38:30]:
Yes. So, there are methods for studying the connectivity of a brain in different scans that you can do to study the communication. Really the fine molecular detail that my lab does so very much relies on these model systems. My studies are the stem cell models from humans. So, you can take patients who, say, have a mutation in one of those genes like the LRRK2 or the PINK1 or the PRKN, and you can generate those stem cells and then you can generate neurons from them, and you can see deficiencies in those or you can even create tiny, so all these neurons can actually, you can create these things called organoids that are like a tiny brain in a dish from that. And you can also study connectivity in that way. So, we do rely heavily on model systems.
But then we can also take, I only mentioned one way of taking patient samples, and that was just doing imaging on them, but you can also take later postmortem samples and you can do things like proteomics, where you can see all the protein character of that brain, and you can see what things are expressed at higher or lower levels. And you can take that back to your model systems, like what I’m working in, and see how that translates, which I think is really important to understanding how this is happening in a whole brain of a human versus in the dish where we’re looking. So, there are ways to translate those things, but again, it is a little bit difficult going from just the brain imaging to the molecular details that we’re looking at here.
Audience Member [40:21]:
Doctor, can you hear me okay?
Dr. Melissa Hoyer [40:23]:
Yes.
Audience Member [40:25]:
Dr. Hoyer, are you looking at any of the additives or the genetically modified food that we consume? Do you have any results regarding any of that as far as disease?
Dr. Melissa Hoyer [40:41]:
So, I personally do not look at any of the genetically modified foods and really the influence of diet on the brain, personally. There are some other labs at the Van Andel Institute that are very much interested in what you’re consuming in your gut and how that relates to how it’s changing your brain. But that’s, I, that’s outside of my expertise. But there are other labs at the Institute that are interested in that very question.
Maranda [41:11]:
Tell us a little bit about your background?
Dr. Melissa Hoyer [41:14]:
Oh, okay. So, my scientific background or personal?
Maranda [41:18]:
Combination.
Dr. Melissa Hoyer [41:19]:
Okay. So, I grew up in the state of Wyoming, and there I kind of learned my love of nature and science and wanting to know how things work from just being out there in nature in Wyoming, by the mountains. I went to the University of Wyoming, and I fell in love with a biochemistry class, and after that I went down to the University of Colorado, and I did my Ph.D. So, I defended my dissertation. And at that point I wasn’t even really working on neurons, I was just looking at those general animal cells and how the endoplasmic reticulum, the green Twizzlers, how it was moving and why it was moving. Just the very simple question of why is this organelle, this endoplasmic reticulum, even need to move at certain times.
And then I wanted to go more into the translational direction, understanding disease, really fascinated in the brain. Around that time my grandmother had a stroke, and she lost a lot of her cognitive function, couldn’t recognize me, and I was just fascinated in how that happens and why that happens. And so, I wanted to join a lab for my postdoc that really studied neurodegeneration and how neurons work. And so, from that experience, it was really great. I really got to learn about neuroscience in general. And that was out at Boston, and Boston was a very active place. You have a lot of medicine going on there. You have a lot of translational research being done at the different biotechs.
But I’m very excited to now be here at the Van Andel Institute, where I feel like it’s a smaller place, but it’s a very highly collaborative place where I can work with different people that even have more expertise in neuroscience than I do, and sort of nurture my creativity and my love and passion for just how cells work, and too, how does these processes in cells really translate to what’s happening in a neuron and then go further to what’s happening in the brain. So, that’s really, I guess my story and my path.
Maranda [43:32]:
You studied at Harvard?
Dr. Melissa Hoyer [43:33]:
Uh, yes, at Harvard Medical School with my postdoc, yeah.
Maranda [43:37]:
Next question. Couple in the room right here. Let’s go for a virtual question and then we’ll move to the middle.
Moderator [43:45]:
Sophie, one of our virtual attendants asks, with frontotemporal dementia, can that be familial? And what might break down in the neurons in that case?
Dr. Melissa Hoyer [43:57]:
Yes, that can be, from what I know about research, and again, I’m not an expert specifically in that field, it can be familial and there are genetic tests that you can do to understand that in terms of the part of the brain that’s breaking down, that is also well known. But I actually don’t know in the case of FTD, what exactly is breaking down.
Audience Member [44:26]:
Great presentation, Dr. Hoyer. Definitely appreciate that. What I haven’t heard on this, and I realize it wasn’t part of your presentation, I think we’ve all heard a lot more about nanoplastics in our food and water. Okay. What do you think’s going on there relative to diseases with nanoplastics? Can you, is that something you can comment on?
Dr. Melissa Hoyer [44:51]:
Yeah, so, I’ve actually been right there with the general public reading the papers that are coming out of labs about this. I find it very striking that they can now, as technology advances, we can begin to detect these very small nanoparticle plastics. And so, we’re opening up and doing mice studies and seeing that it can pass the blood brain barrier. I don’t specifically again research that, but you can imagine if you have even more material that needs to be degraded, can’t be degraded, it likely wouldn’t be a good thing. But again, I can’t really comment onto what the downstream effects of those are, and that’s very openly active research at this point.
Audience Member [45:42]:
Hi, I’m a layman. My name is J.C. Huizenga. And so, I’m gonna ask a somewhat naive question. It seems like your lecture deals with the hardware of the brain, right? So, comparing it to a computer, it’s the software that is the magic that makes the computer come alive. Does the Van Andel Institute also study the interface between the hardware and the software, maybe as an example — dream generation?
Dr. Melissa Hoyer [46:18]:
Sorry, what was the last part of your question?
Audience Member [46:20]:
Does the Van Andel Institute also study the interface between the software and the hardware?
Dr. Melissa Hoyer [46:28]:
Okay. If you think of the software maybe as the genes or the nucleus, is that kind of the right realm of the question? So, if that is the plans, the genes, to make the hardware, the proteins and the organelles, there is abundant research into what happens in that nucleus, that first writes all the software for the plans of the city right there. So, a lot of the different labs are trying to first get at that state of where the gene is mutated and when that happens throughout aging or if it happens at birth, and trying to yes, get at that software level of editing that part. And instead of being so downstream like I am, like looking at the, the degradation after it’s already made, yes. Trying to understand that software part.
Maranda [47:24]:
I love when you were talking about sitting in the dark room for five hours and that just sounds excruciating to me, but you thought it was beautiful.
Dr. Melissa Hoyer [47:32]:
Yes. <laugh>. ‘Cause you can see all the movies that you’re making and yeah.
Maranda [47:37]:
So, when you think about the good work you’re doing here at the Institute, what excites you to keep going every day? To go into the dark room or to do the hard work?
Dr. Melissa Hoyer [47:46]:
Yeah, so, at this point, because as you start your own lab, you kind of pivot from being at the bench, being in the microscope and being that person, to now having the team, and a team doing that. And so right now my biggest driver is my team of people. They give me so much joy and happiness and watching them go through those same steps and seeing those same processes happening in the cell and getting that excitement. So, at this point, watching other scientists be able to look in at the neurons and make their own hypothesis now as to what’s happening in there. And watching that process is really, you know, keeps me very excited every day.
Maranda [48:29]:
We appreciate the enthusiasm. Any other questions?
Audience Member [48:36]:
Dr. Hoyer, Van Andel Institute, I remember David making a comment some years ago. His father had Parkinson’s. I also have Parkinson’s and he said he was gonna have the cure in his lifetime. In the research you’ve done at the Van Andel, what are you seeing? Any perfect good results or so-so results and how do you gauge that? And can you give us an idea of where they’re at? Thank you.
Dr. Melissa Hoyer [49:03]:
Yes. I should have added a slide about what therapeutics have been developed. So, there are different drugs in the pipeline. So, you go through different phases and different tests on the general population. None of them are at the phase that will say “yes or no” how it’s affecting the disease, but there are promising drugs for at least if you have the disease, then having it slow its progression. What I’m trying to do is get at the point of, let’s make things efficient, potentially, before we get to that point where we’re at the disease. So, there’s different areas of how you think about curing Parkinson’s. Do you wanna be able to say, you, you get to the point where you have the disease and being able to really mitigate those effects? But I think starting before you even have Parkinson’s and understanding that will take much more time, and, I think, will be super beneficial because then you never really have to get to the state where you even have the disease. So, each of those points are at different levels. And there is some promise of the therapeutics currently in the pipeline going through clinical trials. But to completely cure Parkinson’s is still on the horizon, in my personal.
Maranda [50:32]:
Any other questions? My final question for you, Van Andel Institute we always say 100% hope. What gives you hope as you study the brain?
Dr. Melissa Hoyer [50:45]:
Yeah, so just being able to see the progress from when I was a graduate student to now, and understanding how much more we know about the brain. And we so at first, we knew that we had these Lewy bodies, they had alpha-synuclein, but now we’re being able to actually look at what else is around them, and see that there’s damaged organelles there. So that opens up another field, and that, just being able to peel back the intricacy of the disease and how fast we’re doing that gives me a lot of hope. And how we’re really harnessing the technology and how fast that’s going and then being able to apply it to the disease. That’s what gives me the most hope.
Maranda [51:28]:
Excellent. Let’s give Dr. Hoyer another round of applause.
If you are interested in finding out about more, more about the work that she’s doing along with all the things happening here at the Institute, you can find it on the website vai.org. After today’s presentation, if you are joining us in person, we have two of our lovely friends here who would love to give you a tour of the facility where you can kind of peek into some of the labs and get a sense of what really happens here. This is the first of our Public Lecture Series for 2025. We have another one in May, and then several more coming up. Find that on our website again. What a great way to just get a little sampling of the things that are happening here at the Institute every single day. Thank you so much for joining us and I hope you have a great day where you live. Thank you.