Molecular Alternatives to Alzheimer's Disease Research
Maria Losito
Welcome to a special episode of Interview with a Biologist. I'm your host, Maria Losito, and I'm joined today by Dr. Brian Ackley, who is professor of Molecular Biosciences and co-director for the Undergraduate Biology Program at the University of Kansas.
Through an effort led by Doctor Michael Wolff, a W.M. Keck Foundation grant was awarded to three scientists at KU and one at UC Irvine. Brian is one of the collaborating researchers on the project, titled In Search of Molecular Triggers of Alzheimer's Disease, which aims at testing molecular alternatives to the prevailing amyloid hypothesis of Alzheimer's disease. Thank you so much for joining me today, Brian. And congratulations on your grant.
Brian Ackley
Thank you so much. I appreciate your time.
Maria Losito
So would you mind explaining the amyloid hypothesis and then tell us more about the alternatives that your work is testing and result in regard to Alzheimer's?
Brian Ackley
Sure. So amyloid hypothesis has been the sort of dominant way we have tried to explain the onset or the causes of Alzheimer's disease. And really, we can kind of break all simmers disease down into two main categories. There's the early onset, which has a strong genetic familial linkage, and people who get who have inherited one copy of a couple of different genes with mutations in it will almost assuredly develop Alzheimer's disease, often as early as in their 30s.
Sometimes it's in their 50s. More commonly, though, is what we call late onset or sporadic Alzheimer’s disease. Despite having different kinds of genetics behind them, they both share a characteristic that, upon autopsy, humans have often high copies of a protein plaque made of a protein called amyloid. And so it was in about the late 90s that scientists cloned the genes that cause familial Alzheimer's disease.
And it turns out one of them is an enzyme, and the other is in the substrate that make these amyloid plaques. And so the prevailing hypothesis has been that what happens in these mutations is that they cause too much of the precursor protein, the amyloid precursor protein, to be made or changed the cleavage such that the product will assemble into these plaques versus the other cleavage product, which will not.
And that that then those amyloid plaques are what initiate disease over time. And that has been the prevailing hypothesis, except that there have been a number of maybe we can call them either cases or exceptions. One of them is, is that there are plenty of humans with Alzheimer's disease who display almost no plaques. The second is that there are people walking around who have many plaques that would qualify as sort of diagnostically having Alzheimer's disease, who don't display clinical manifestations.
And more recently, scientists have developed antibodies that are relatively effective at clearing amyloid plaques from brains. But that hasn't really shown up in any rescue of the cognitive deficits that people with Alzheimer's have. And so, we and this is not unique to us. There have been a lot of people who have been sort of concerned that the amyloid hypothesis is incomplete at best or wrong, and that maybe the plaques are, you know, sort of where the light is and where the disease is coming on is earlier.
And so, this new grant is really trying to understand why do these two proteins that are present in humans and actually their ancient. So, if you go evolutionarily back in time, they exist in organisms all the way back to like the earliest multicellular organisms. Why do those proteins, when mutated in this particular way, result in Alzheimer's disease if it is not the plaques themselves? So that's really the basis of the new grant.
Maria Losito
So your grant mentions molecular triggers. Would you mind diving into that a little bit deeper and telling us what kind of things or triggers that you look for.
Brian Ackley
Sure. So, in this particular grant, the lead investigator, Michael Wolff, was one of the first people to actually discover that the presenilin-1 gene, which encodes a protein called gamma secretase, is an enzyme. And what it does is it basically sits in the sort of the top layer of our cells facing the outside of the cell, and it cleaves proteins in a specific way as they exit the cell.
And so, his understanding of that has led to this idea that really generated this amyloid hypothesis. So, this gamma secretase protein forms a complex. So, it's one of four proteins that's in the part that does all the cutting up of the substrates. And what happens though is, is that when he went back and tried to more formally test the main sort of principle of the amyloid hypothesis, he found some discrepancies.
So, if you were to sort of ask a person who works in all Simons disease about the amyloid hypothesis, what they would generally say is that the mutations result in a cleavage product that is 42 amino acids long, whereas the non-mutated forms lead to a preferentially formation of a 40 amino acid long peptide. And then if you take the 40 amino acid peptide and watch it, put it in solution, do whatever you want with it, it won't form plaques, whereas the 42 will form plaques.
Who knows why? Some biophysical reasons but the hypothesis is long proposed that when you have these mutations or some other stochastic event in the sort of like late Alzheimer’s disease, it shifts the ratio so that you make a lot more of the 42 version than the 40. So he went back. Mike went back and very stringently analyzed what happens to the cleavage products when you feed normal substrate to mutant enzyme or mutant substrate?
These are the mutations that cause familial Alzheimer's disease to normal enzymes. And it turns out that in some cases, yes, you can see that the ratio shifts in line with the amyloid hypothesis. But really, genetically speaking, the mutations that lead to the earliest onset of Alzheimer's disease actually reduce the total product made. So while you might end up with more 42 than 40, you wind up with 1000 fold less cleavage product.
And so that did not seem to reconcile with the idea that you just have to make enough of this bad, you know, amyloid in order to cause the disease that really this reduction in the activity of the enzyme was tied to the sort of severity of the outcome. So, we've known for a long time, though, that if you make a mutation that basically just prevents the enzyme from working at all, or you use drugs that basically block the enzyme from working at all.
You don't get people with Alzheimer’s disease. You get a developmental or a skin disease for other reasons. So that means that you can't invoke the idea that these mutations just cause the enzyme to stop working. Something else has to happen. So Mike and his colleagues, including me, we have been lately looking at this idea that instead of not working, that what happens is when the mutated enzyme or substrate meet the normal enzyme or substrate, they kind of get locked into this sort of what we call a trapped complex, and that just doesn't work very well.
And that trapping of that complex, in essence, is the trigger and so we do have some evidence for this. Mostly in inside an organism comes from the work that we started with, with Mike and I’s first collaboration, and that was to create these lines of these animals that I use called C. elegans, where we could actually look at things that happen inside people with Alzheimer's disease, namely, what happens to the nervous systems in people with Alzheimer's disease?
So sort of categorically what you would see if you got onto the Alzheimer's Association website is that people with Alzheimer's disease, their brain becomes sort of shrunken, full of holes, and really through this sort of degeneration of the neurons loses volume over time. That is true. That is what happens in people with late onset or with late-stage Alzheimer's disease.
But early on before people do, you know, have this sort of broad neurodegeneration. We know that synapses, which are sort of the gateways that allow us to think and feel and do all that sort of stuff that are inside our brain, that those are the vulnerable parts, that those begin to disappear early in the disease, what we call the prodromal phase.
Before people would go to the doctor and tell them that they have these strong memory losses. So, we created these small nematodes, which I'm happy to talk more about, so that we can look at the synapses in living organisms, and they live a very short period of time. So we could create models of these complexes that can form but can't produce amyloid versus the complexes that can form and can produce amyloid.
And if we insert one of these mutations that causes FAD in humans into these small C elegans, what we see is that as they age, they show degenerating synapses. And then if we create a version that makes amyloid, they show degenerating synapses. But then if we create new versions of those substrates that can still that still have the FAD mutations but cannot produce amyloid through another trick they still show generating synapses.
And in fact, they show it faster with an earlier onset. And we'd shown through other means that what happens is that even though it can't cut these things into amyloid, it can still form this sort of trapped complex where the substrate sort of stays in that enzyme for a lot longer period of time. And through some other work that we're currently following up on in this particular grant, what we think is that that that complex is sort of a beacon for the cell to like something is wrong, and it's that sort of something is wrong signal that is actually causing the synapses to degenerate.
So that's sort of what we mean by a trigger. We think this new trigger that explains a lot of the things that the FAD mutations can cause this particular disorder or these sorts of phenotypes in C elegans, but also explains the data that we have found from other kinds of systems where it really is this enzyme, if you want to think about it like a pencil sharpener, is what I've always thought about it as.
So. So it sort of trims this amyloid into multiple smaller pieces as it's sort of going through. But instead, if you sort of like stuck that pencil into the pencil sharpener and it was either too large, you would hear it sort of grind a little bit more slowly, and the pencil wouldn't sharpen as quickly. And if it's bad enough or you have the wrong sort of like material in there, it actually could jam the pencil sharpener.
So that's how we're kind of thinking about it. And that sort of like grinding noise that the pencil sharpener might make upon, you know, sort of that trapping is really the cell going, Whoa! Maybe we should take some action here.
Maria Losito
So, the overall research utilizes mice and human iPSCs or induced pluripotent stem cells. How do you plan to use this combination of models to advance research in Alzheimer's disease?
Brian Ackley
Yeah. So, this is a really cool part about this. This is one of the things that, again, having worked with Mike for a couple of years, KU recently recruited another scientist, Dr. Jesse Wiley, whose expertise is in the use of these induced pluripotent stem cells. So we can take human cells that can be basically turned into any kind of tissue that we want, and we can give them specific instructions to make neurons, all other kinds of cells that we think might be involved.
And we can engineer those to have these mutations, these familial Alzheimer's disease mutations, or to not have them. And then we can sort of compare in parallel the consequences of having those. And Jesse's work has really been pioneering in the idea of asking, once you induce these mutations in these cells, what happens on what we call an omix level?
So what happens to the gene expression patterns? What happens to the metabolomics? What happens to all these proteomic structures? We're doing this in parallel. So, my lab will be doing this using these C elegance nematodes that I mentioned earlier. So, we'll take these same mutations. We will basically look at the neurons and ask what happens at a level across the entire organism.
In collaboration, Doctor Kim Green at UC Irvine is basically doing the same thing in mice. So as I mentioned earlier, these proteins, these genes that that encode these sorts of gamma secretase proteins and this amyloid precursor protein are ancient and they're very highly conserved. In fact, what we first learned about how gamma secretase works inside an organism came from C elegans.
It was the first functionally characterized mutation in a gamma secretase gene. And so what we can say is, is that if we take the human version and we put it back into a worm where the gamma secretase has been mutated, the human protein can completely rescue it. So that means it functions the same inside a worm as it does inside a human.
And as I mentioned, C. elegans have synapses. And synapses work basically the same way. They do all of the things, and worms use the same kind of neurotransmitters. So our idea here is to think more vertically, and that is if in fact, these proteins function normally or they are equivalent functional in in worms, mice and human cells, then the responses to these deficits that are induced by these mutations should also be relatively conserved.
And so one of the things that happens inside people is when we try and do these studies is, is that all of these humans wandering around, they have may have these familial Alzheimer's disease mutations, but everything else about them is going to be incredibly divergent at the level of human diversity. And so, if we're looking for conserved things, we have to take into account, you know, family history and all that.
And there are a lot of really great scientists who are working on that. So, we hope to reconcile our data with theirs. But it's very sort of needle in a haystack. So what we're trying to do is reduce that genetic diversity and look for these sorts of conserve things. So, what kind of signals come out of C. elegans with these FAD mutations, sort of signals come out of mice with these FAD mutations.
And what sort of signals come out of human pluripotent stem cells? And then if we can sort of find the Venn diagram that those are, in our minds, most likely to be causing or at least contributing to these sort of genetic, you know, conditions, then using these sort of easily and somewhat ethically modifiable genetic systems, we can go back and ask, say, hey, when we induce these FAD mutations in C. elegans and mice and induced pluripotent stem cells, we see this signature pathway.
Let's go in and sort of like mutate that signature pathway and ask does that change the outcome. And again, the sort of nice thing about having these multi-systemic processes is we can really hone in on the things that are sort of like most convenient to look at. So, for example in the ceilings we can do this relatively quickly because that synapse degeneration phenotype that I talked about that happens within a week of the animal becoming an adult. In mouse,
That's about 6 to 12 months. So we can screen, you know, 52 different things in a year, which would take them longer. The induced pluripotent stem cells are somewhere in between. So, we have a higher throughput in one than the other. The complexity sort of scales though. So, when we're doing this in worms, we're looking at something that has 300 neurons versus mice that have, you know, a couple of billion neurons.
So, between those sorts of tools, we can really try and hone in on these things that are perhaps explaining the disease. And then, you know, if we can find a pathway that might explain the disease, we can try and think about what are the ways that we might be able to sort of like work towards fixing that. And so that's a longer-term goal. Right now, we're really trying to understand the etiology of the disease.
Maria Losito
With your work with C elegans what other areas do you see this impacting?
Brian Ackley
Yeah. So that's a really great question. So, my lab has been working on multiple different kinds of ways to affect synapses. That's really what my training in is trying to understand like how do synapses develop. And one of the things that happens inside our brains every day this is a simple way to think about this, but it's pretty consistent.
And that is we build up a bunch of synapses. Just say you build a million synapses during the day, and then we go to sleep and our brain goes in and it prunes out the unnecessary ones. So the next day when you wake up, you might have 10,000 new synapses. So that process of building synapses, eliminating synapses is actually an incredibly normal process.
And we think for lots of reasons, that many neurodegenerative diseases, including Alzheimer's, might have this system sort of gone awry. And so, one of the hopes, though, is, is that if we can get into the prodromal phase and understand what is driving this sort of like reduced addition or exuberant elimination that might be underlying the loss of synapses, that this is actually when there might be a reversible phase, because we kind of know that that synapses are a little bit they're very metabolically costly.
Our brain uses a lot of our energy. And one of the reasons that we this is now much more hypothetical than we have proof for. But one of the hypotheses might be that in these systems that are being stressed by these molecular triggers, that they might sort of reduce the total number of synapses temporarily to sort of try and clear that metabolic imbalance and then restore them afterwards.
And there's some evidence from that from like hibernating animals and sort of thing. So again, what we're trying to think about is like, well, how do synapses get added normally? How do they get eliminated normally, and how might they be restored? And that's really what my work had focused on until I started working on this particular add pathway sort of work.
So, what we want to understand is synapses in general. And the nice thing about C elegans, as I mentioned, we have a lot of genetic tools, but they're also transparent. So, we don't actually need to.
Dissect them in order to get at these synapses. We can look right through their clear bodies and see them and count them and look at what they look like and whether they come back. And we can do this over time. So those techniques are really empowering us to both understand how normal events happen. How they're affected by disease states, and what might happen if we could resolve that disease state.
And so just that sort of fundamental understanding of the process is really going to help us not just understand Alzheimer’s disease, but it might be relevant to other kinds of neurodegenerative diseases or just aging in general. I would assume that that most of our listeners are probably going to be thinking about like, well, I would like to maintain as many of my, you know, synaptic function or cognitive abilities.
The older I get. And really, that's one of the things that we're trying to understand is like, why do some people or some organisms sort of age gracefully and some maybe not so much? What are the processes that sort of stochastically affect that? And again, that's why I think these small, genetically powerful animals are so good at this.
They have a normal lifespan of about 2 to 3 weeks. And so, we can watch things happen over very small amounts of time.
Maria Losito
And so, this may be outside the scope of your work, but would you say that the sort of redevelopment of synapses would also have an impact on something like TBI or traumatic brain injury?
Brian Ackley
Certainly could. So, the other side of my lab that works on one of the AD things works on a protein called tau. Tau is also mutated in is not mutated, but also polymerases. In Alzheimer’s disease, it can be mutated in a number of other neurodegenerative diseases that we call primary tauopathy. So, mutations in Tau cause progressive supranuclear palsy, frontotemporal dementia, etc. it is implicated, though, in traumatic brain injury and chronic traumatic encephalopathy, where damage to the brain can induce this sort of like again, reactive tau polymerization and then can be a long-term consequence on the brain.
And so, what we could hope for would be that if we understand again thinking about the reaction. So, a lot of us understand that. Like if we get bruised on our arm that there are some swelling and the swelling is helpful until it's not, and then it becomes inflammation, which is bad. So, at what point in, say, a traumatic brain injury or chronic traumatic encephalopathy, do you go from a reaction that is protective to one that is not protective?
And when do you go from not protective into sort of like beyond repair. And so those are difficult to measure again, in humans or mice or some of these other sorts of like commonly used organisms to look at those time points. You have to sacrifice the model system. We don't do that with humans. But so with these sorts of model systems where we can look at those sorts of events and see at what point do those things cross in between those thresholds, that would be a use that some of or like.
We would hope that the data from our science would, would help, you know, uncover some of those time points where they could be investigated in those other systems.
Maria Losito
You've mentioned that C. elegans are transparent and that because of that you have an easier way of interacting with them, studying them without having to go to dissection. I imagine that these are very, very small creatures, how do you find that out?
Brian Ackley
That's great. Great question. So yes, they are when fully grown about one millimeter long, the most commonly suggested, you know, equivalent is like a comma on a page. And when they're first born there are about a quarter of that size. So, we do everything under a microscope. But we take advantage of the discovery of the green fluorescent protein and other related proteins that it turns out we can just sort of molecularly glue those onto other proteins.
So, for example, in my lab, we use a reporter. So, it tells us things about the cell in which we have taken a protein that goes only to synapses. We've glued on this green fluorescent protein and then we've engineered it. So, it's only made in certain neurons. And then we can see each individual synapse within these animals. And then what we notice is, is that if we count them, the entire animal on one side of its body has about 150 of them when they're full-grown adults.
And then if we start messing with these FAD mutations or these tau genes, then over time that starts to decrease, and it decreases with kinetics that are relatively normal. And we can then also measure things that make that better or worse by looking at those curves. So it really is this powerful tool of using these fluorescent proteins, very powerful microscopes with lasers, which are always fun and then really just patience.
Maria Losito
So, before we kind of move into sort of like the outside question, is there anything that you can think of that we haven't touched on that we should.
Brian Ackley
The only thing I think is that within these animals, the other thing that my lab is also interested in is, is thinking about how the entire nervous system develops. And one of the things that I think is, most interesting about aging is what it looks like in some conditions. We are reiterating earlier normal developmental events inappropriately.
So one of the things that we're looking at right now is that we know, for example, that there are these proteins that come turn on inside neurons to basically say, hey, make all the proteins you need to be this kind of neuron. And then another sort of like process comes on to sort of like cement that and keep that process going and that in some degenerative diseases or aging conditions, those early proteins that should be restricted only to when the nervous system is developing, sort of come back on.
And so again, with these sort of fluorescently labeled genes, what we're trying to look for is, is that the reappearance of earlier developmental processes that might indicate that something has sort of gone from, should be turned off to being turned back on. And I think that that's just another sort of like way to consider aging. A lot of us think of aging in the field as sort of like this shutting off of normal processes, but the inappropriate turning on of earlier developmental processes could be injurious as well.
And so we are trying to look for these sorts of like steps that should be completely quiet but have turned back on. And that actually might be something that is one of those things that very early on, as these neurons are trying to repair themselves, those things are coming on correctly. But then the neuron decides, oh, wait, I'm both aged and I'm expressing sort of like developmental things.
I'm just going to give up. And, you know, it's better to sort of like, clear myself from the brain. And that might be where humans trip from this sort of like only synapses are being affected to cells dying. So that's another thing that we're hoping to try and understand what these models that now that we have multiple different versions of these, we can go back in and ask,
Maria Losito
How will this grant impact your work outside of Alzheimer's disease? Do you foresee this research impacting other areas of human health?
Brian Ackley
Yeah, I think that some people have thought of this idea that if we all live long enough, will develop Alzheimer's disease, which is a little bit probably spurious in the sense that all dementias are not Alzheimer's disease. But I do think that as we think about, again, what is normal aging and how do we then sort of improve health span during normal aging?
That would be sort of a bigger picture question that we're trying to work on in my lab, because our brains are these incredibly powerful, functional units that we have honed to become the dominant species on Earth, and yet they seem to be one of the things that that sort of betray us the most as we age. And if anyone has lost a family member or watched a family member go through dementia, it's heartbreaking.
If you read on the Alzheimer's website or you just think about aging in general, we lose both human connection to people with these sort of dementias, and there's a huge socioeconomic cost as people have to quit jobs to caretaker for aging parents or, you know, loved ones. And so really just trying to understand the fundamental aspects of helping organisms and mostly humans, age more gracefully.
I believe that our work fits into that, both from the multiple things I've talked about specifically with this grant, but in general, how the lab is working on that.
Maria Losito
That's really fascinating. And this is just kind of a sidebar. We took our dog into the vet recently. She's 13, 14 years old and has been slowing down mentally. They have this new thing that I think they're originally testing for human livers that in dogs helps with cognitive like degenerative like.
Brian Ackley
Yeah.
Maria Losito
And it was just wild to me to think like that. They were making that for animals. And then it's just like all that research wasn't just going into human study.
Brian Ackley
So this is again thinking about the for a long time from an Alzheimer’s perspective, the amyloid hypothesis helped us immensely to sort of like connect some of these physiological processes. At some point, it tripped from a hypothesis into a hegemony that has sort of like blocked the identification of other approaches in ways that have been, I think, injurious to the process of science.
One of those things is that the gold standard has been we’ll try therapies in mice who have these sort of prescribed or maybe like overburdened amyloid pathologies. Whereas there are these somewhat we call natural models. Right. And so, dogs they develop cancers and mice generally do not develop cancers unless you give them these different kinds of mutations.
Dogs, it's easier to tell when they have cognitive difficulties because we are around them all the time. And so, it's harder because they live ten, 12, 14 years and people don't want to just start giving like screening compounds in dogs. Right? But there are a lot of people who I think are trying to take these models and just say, okay, we learned about this here.
Where are some places where we don't have to engineer things, where we can sort of somewhat humanely test them in conditions such as that. And you mentioned that this sort of idea of the liver. So, I talked about earlier how our brain uses so much of our energy. And if you were to do a functional energy scan, a Pet scan of humans, the liver and the brain basically use 90% of our energy.
And so, if people are in end stage of life, organs will shut down as the body tries to sort of like process energy to, to maintain those things, you know, sort of the Star Trek diverting all energy to shields and engines. Right. And so, one idea might be that if those processes that are doing that are basically diverting energy from the brain to the liver, then metabolically the brain would sort of thing.
So, if you say, well, the liver doesn't need that much energy, right? It's just sort of these pathways. Can we sort of slow that down a little bit, send more energy back to the brain? That's just a sort of like back of the napkin way. You could say that just might help. And if it doesn't help, then you've not really done much harm to somebody that's that much older.
Maria Losito
Fascinating. So back to the grant. What way will this grant support students in the lab?
Brian Ackley
So I run a research lab in addition to being a professor who teaches in classes. That's really one of the most exciting parts of my job is being able to train the next generation of students. So the grant will support graduate students who are working on their dissertations in the lab, and it'll also support undergraduates who are going to be learning about how to do science.
So as I mentioned, we have these genetic models, and we can count these synapses under these microscopes. And so, we have a couple of graduate students. So, one of the graduate students in my lab right now, Caitlin Lebowitz, is been pioneering a lot of these particular models. And she works with a couple of undergraduates who are doing some work for her.
So, they are crossing these mutations into different genetic mutant backgrounds or are sort of counting some of these sorts of synapses to really try and help her move her research along. And then she sort of helping move our research along. She's mentored by both Mike and I and another student, Nathaniel Amasa. He is a younger graduate student in the lab, but he is just getting started where he is trying to break down these developmental pathways to ask if those things are influencing the activity of these synapse degeneration pathways.
So those two students are working on this as part of their dissertation projects. And then again, as I mentioned, we have undergrads who come in and they really get to chance to complete projects that contribute to these, you know, the success of the grant and for students who are interested in sort of nervous systems and again, for people who have been around student or family members with these degenerative diseases, it really helps them to be thinking that what they're doing is contributing to the embarrassment of society.
And so it's really been helpful to be able to say to them, yeah, this project is now picking up steam because for many years before we got this grant, we were doing this on what we might call the shoestring budget of really trying to keep things sort of, you know, humming along without a lot of, you know, grant funding.
But what the heck Foundation has done is they recognize this, this truth, that there are a lot of headwinds to developing models that go counter to the amyloid hypothesis, and that we had demonstrated through our preliminary data that we just might have something. And it's risky, but it might be a huge benefit to society to truly understand whether these triggers are the cause of Alzheimer's disease or a cause of Alzheimer's disease or are not.
Right. So if we eliminate things that's beneficial, it maybe doesn't drive the field as far, but just if we do figure one of those things out, then all of the people who have contributed to it have sort of like built these, you know, these blocks into this sort of like proof that is helping society.
Maria Losito
Beyond this grant your research lab and the classes you teach, you're highly involved in student development at KU. What can you tell us about the involvement with professional development of undergraduates and grad students?
Brian Ackley
That's a really great question. So, science, what I tell my students is this science is a set of tools to try and answer complex questions. In the same way, in the kitchen, you might have many different knives or many different, you know, ladles or spoons or pans or pots that really trying to figure out what the combination of those things need to go together to make your meal is, is a skill.
And so, learning how to ask good questions in the lab is really what I want students to be able to do. And so how do you break down complex ideas? How do you begin to understand what people have done previously to try and answer these sorts of questions? And so, installing those ideas into students, especially when they're younger in is an undergrad and then moving on into grad students and those questions get more complex is part of what I think is a great thing about being a professor.
The other thing that's awesome, right? As I mentioned, these worms they glow and you put them under a microscope, and you get to see their neurons. And the first time you see these students look at this and they go, wow, right? And then they have that sort of like epiphanic moment that that science is, is really cool. And then I trap them by basically telling them at some point they're going to be sitting there at the microscope and they're going to see something, and they're going to realize that they've discovered something and they are unique.
They know something that no one else on this planet knows. Now, our next job is to tell the planet about that by publishing our research or doing these sorts of podcast things, but really that they can sit there knowing that they know something about the world that nobody else knows. And then I've got them hooked. Right? This is the way that they think about it.
And so, seeing those students develop and then what do we do next? And then we work on things like sorts of writing and presenting and, you know, honing those sorts of ideas. Hopefully then they're going to take that toolkit if they are undergraduates and go on to either graduate school or medical school or some other kind of business, if they are a graduate, students are going to move on to postdoc or industry, and that we sort of like keep that kind of like pipeline going where students are really learning.
Foundationally, how do we ask good questions? How do we create good experiments, what kind of controls do we do? And moving that on? But back to the sort of like original question like in that development phase, I also tell them there are very few jobs out there. You might choose not to be a scientist, but any job you can think of, there are probably big, complex questions that don't have answers yet.
And I've never had a CEO of a company tell me we have this multi-million-dollar problem it's costing us, you know, every year, but don't try and solve it. We just love losing money. Right? So, if you can take this toolkit, this sort of like breaking down complex questions, figuring out what people have tried before, testing those things and evaluating how that works.
You can apply that to any business that you might choose to want to do. And so again, for students that are coming to Ku or going to another university to get involved with research, just to learn how to do that, because I guarantee you, no matter what job you take, at some point someone that works for you is going to bring you something and go, what do you think of this?
And if you have the capacity to ask intelligent questions, to sort of figure out, like why they're bringing it to you or what to do with it, those are just lifetime skills.
Maria Losito
Yeah no, can confirm. Critical thinking in that skill set has been a great thing for me to learn and to implement throughout life. So. All right.
So you are also involved with K-INBRE or the Kansas Idea Network of Biomedical Research Excellence, which is an excellent opportunity for students. What is the best way for those interested to apply? And then can you tell us a little bit more about that program?
Brian Ackley
Sure. So, the K-INBRE is a statewide grant. It is administered to Kansas by the National Institutes of Health with the idea of stimulating biomedical research writ large across the state. And one of the foundational parts of it is, again, that sort of student training aspect. And so the grant makes sort of awards to ten different universities across Kansas with the idea that students can come in and work in research labs.
They don't necessarily have to be trained when they start, but really, they do need to be working in a research lab. So, for people who are in a research lab, what we can do is provide a scholarship that helps them pay, be paid to do that research. And that's important because a lot of the time, in the absence of that, people have to volunteer their time to get experience.
And not everyone really has the sort of like capacity. So obviously college costs are going up. You have to pay to, to live, apparently. I mean, this is crazy. I mean, we're asking people to pay rent and for food and, you know, but when you ask students, do they want to get involved in research? So many of them just want to at least come into a lab and see, is this something that is right for them?
But they don't get the opportunity? So, the K-INBRE is really trying to help them to do that. And so we pay for students to do that at Ku. And then once a year, we get together at a statewide symposium to allow students to demonstrate their research to other people, to talk about it, to present their posters, to give talks, etc.
So, it really also offers them that scientific conference experience. We have a website, kinbre.ku.edu which has the application. We take applications once a year, typically around January. So people who are in a lab in the fall and would apply then and then they would start in the summer. And if they are at other Kansas Regents institutions, they will have a slightly different schedule.
But they will have the same basic process you would apply to, to be a part of it, and then you would get that award that would pay you for your time for the next calendar year. My contact information is on that website. Or they can go to the parent K-INBRE website and get other information about other places to contact.
And the people who run these, both at KU and at other places, are really interested in talking to those students about the fit and about the expectations to make sure that people understand what they're getting themselves into.
Maria Losito
Brian, thank you so much for joining us today. I really appreciate you giving us a deeper look into your research, this grant and all the ways that you help students at KU
Brian Ackley
Thank you so much for talking to me, I appreciate it.
Maria Losito
Thank you for listening to Interview with a Biologist. You can check out the show notes for more information about Doctor Ackley’s work, as well as a link to the research paper discussed in this episode. A full transcript of this episode will be available at biology.ku.edu.