00;00;09;17 – 00;00;47;02
维多利亚之声
Welcome to Beyond Lab Walls, a podcast from the Salk Institute. Join hosts Isabella Davis and Nicole Mlynaryk on a journey behind the scenes of the renowned research institute in San Diego, California. We’re taking you inside the lab to hear the latest discoveries in cutting edge neuroscience, plant biology, cancer, aging, and more. Explore the fascinating world of science while listening to the stories of the brilliant minds behind it. Here at Salk, we’re unlocking the secrets of life itself and sharing them beyond lab walls.
00;00;47;05 – 00;01;14;20
伊莎贝拉
Welcome back, listeners. I’m Isabella, and today I’m joined by Aksinya Derevyanko. Aksinya is a molecular biologist currently working in the lab of Professor Nicola Allen here at Salk. She’s interested in the microscopic connections between the neurons in our brains called synapses. These synapses are where messages get exchanged between neurons and are the foundation for healthy brain function. Now, Aksinya is asking what happens when these synapses dysfunction.
00;01;14;22 – 00;01;31;06
伊莎贝拉
And in particular, does that dysfunction relate to Alzheimer’s disease? And if so, how? But before we get into all of that and her science, let’s go back to the beginning of her story. I’m very excited to be chatting with her today. Welcome to the podcast. Tell me, where did you grow up?
00;01;31;08 – 00;01;54;06
Aksinya
So yeah, I was born still in the USSR and I grew up in the Altai region. And so in my family, my parents were not really researchers. Well, my dad, he’s like a creator. He’s an artist. He’s a chemical engineer. He also did like a line to recycle and repurpose plastics. So he’s just, like all over the place.
00;01;54;08 – 00;02;25;27
Aksinya
And my mom, she was a mathematician. But when USSR collapsed, many institutions, they had to downsize, especially in Far East. So many scientists had to repurpose. So my mom did, and I kind of benefited from that because most of my teachers in high school were like nuclear physicists or plasma physicists. My parents put the importance of education, because education in my country is very accessible to everyone, and it’s almost free.
00;02;25;29 – 00;02;49;24
Aksinya
So you just need to study. So their approaches were very interesting. I think first they got me enrolled in a job, so like, service oriented. So like age of maybe 13 I was working 24 hours shifts at the gas station, which I was totally on board with. And I think it was great experience, which also helped me understand how hard is the job market.
00;02;49;24 – 00;03;14;24
Aksinya
That some jobs are lower paid than others. And if I want to do some more creative type of things, with all my respect to gas station workers, I, I have to pursue my education. And another fun thing they did is that they went and do the master’s degree to show us that you should always study, personal development. And it was fun to go to school the same time as them.
00;03;14;26 – 00;03;24;07
伊莎贝拉
That’s so funny and sweet to be in school with your parents. I would have loved that. So you knew you wanted to focus on your education, but did you know you wanted to do science?
00;03;24;08 – 00;03;49;24
Aksinya
I wanted to become a linguist. I didn’t think of being a scientist just yet. So I tried to enroll in Moscow State, and I went there and did my exams like three times. And, with a system where you can study for free, you need to compete sometimes with the whole country. So I couldn’t get in, which I fulfill that linguistic dream later on since I travel and learn couple of languages.
00;03;49;26 – 00;04;14;04
Aksinya
So then my plan B was I didn’t really have a plan B, so I was going by mattered by contradiction, let’s say. So take into consideration we finish high school pretty early. So I was like 16. So it’s very early age to take that important decision. So I was thinking what I don’t want to do and don’t want to pursue.
00;04;14;04 – 00;04;37;15
Aksinya
And then life sciences sounds interesting because it’s about life. It must be exciting. So I, I considered Novosibirsk State University, which is famous in Russia for its departments in STEM. I passed entry exam, I got admitted, and then I went to admission committee. And it is important to have a really good friend because I brought my friend with me.
00;04;37;18 – 00;04;54;01
Aksinya
And when I come in, they say congratulations. So what department do you want to join? Biology or chemistry? I look at my friend, very good friend, and she said, of course, biology. So I turned around and say, of course, biology. And here I am.
00;04;54;01 – 00;05;03;08
伊莎贝拉
That’s so funny. The best way to make any decision, just relying on your friends. So you started in biology and then how did you end up interested in neuroscience?
00;05;03;12 – 00;05;24;22
Aksinya
Right. So as soon as I got into university, I quickly realized that all my peers are very familiar with what is to be a researcher. For example, many of their parents were researchers in the institutes around or there was high school associated at that university. So as soon as I could, I tried to get my first lab experience.
00;05;24;22 – 00;06;11;26
Aksinya
So the first lab I actually got in after the course of Botanics was in Siberian Botanic Garden. I did a project there and in the Institute of Organic Chemistry, where we study mushrooms and we prepared different types of extract. My studies were going on and I realized I’m really excited about molecular biology. So I talked to my, yeah at the time, explained her my interest, and then she introduced me to her friend who was running a lab in the institute across the street, which was Institute for Chemical Biology and Fundamental Medicine, and my first molecular biology, PI, Zharkov Dmitry Olegovich, he introduced me to the biology lab world.
00;06;11;29 – 00;06;38;25
Aksinya
He taught me all the great skills; how to design the experiment, the lab ethics, how to approach your time management, and all sorts of things. So I’m very grateful to him for that. And then he was also the one that introduced me to the synapse, which I’m actually working on right now, which is, the synapse is this connection where neurons transmit signal one to another.
00;06;38;27 – 00;06;57;24
Aksinya
So he explained what it is for us in the course of molecular pharmacology as an example, with Botox.
00;06;57;27 – 00;07;25;00
Aksinya
So I was working on the project where I look how DNA repair mechanism can lead to expansion of three nucleotide repeats, which is a trigger of many neurodegenerative disorders, such as Huntington’s disease. And so we did not have a class of the neuroscience at the university. But that sparked a lot my interest. And since then, I always wanted to know more about how the brain works and all these diseases develop.
00;07;25;00 – 00;07;48;09
Aksinya
And then — my first PI — he also presented me with amazing opportunity and I’m so thankful for that. We found friend’s lab in Villejuif, near Paris in France, which were also working on the DNA repair so I could do three internships and do portion of my experiments in their lab. So I was able to visit international institute and see how differently things work.
00;07;48;11 – 00;08;28;02
Aksinya
And I quickly realized that for me, it is very important to have this diverse experiences in science and in life in general, which was not necessarily how things were working back in Russia. But I realized it’s quite important to get to learn as many things as you can and to see all different labs, meet different people. After having this realization that I want this international expertise, and that I’m interested in translational research, I started to apply for fellowships abroad and I got one actually in Spain, in Madrid.
00;08;28;04 – 00;08;45;21
Aksinya
So that’s where I first moved to do my PhD before coming to the United States. And the lab in Madrid, it was great lab that was working on telomere biology in the context of aging, cancer, and other diseases, run by Doctor Maria Blasco.
00;08;45;23 – 00;08;48;02
伊莎贝拉
And what are telomeres?
00;08;48;04 – 00;09;12;03
Aksinya
So telomeres are these repetitive sequences that form caps on the end of the chromosome. Because if you think the chromosome is like double strand DNA. So if they are not hidden, they can be recognized by DNA repair machineries. And this can trigger DNA repair. So chromosomes can be fuzed or it can signal that there is a damage and cell will go to senescence and die.
00;09;12;05 – 00;09;16;12
Aksinya
So it’s very important topic in the field of aging.
00;09;16;14 – 00;09;23;20
伊莎贝拉
So then you started doing this telomere research in Spain, in Madrid. How’d you go from Spain to San Diego?
00;09;23;25 – 00;09;53;07
Aksinya
Right. So now my main project, which I did on aging, I also did several collaboration with within the lab and other institutions as well, where we touch on neurodegeneration. And this reminded me about my spark in the neuroscience research. And then I started to look for a lab in neuroscience, which are looking at the people who are looking at all these different cell types in the brain and in the context of health and neurodegenerative diseases.
00;09;53;13 – 00;10;19;21
Aksinya
That’s how I got here at Salk and got into Nicola Allen’s lab. Actually, I learned about San Diego during my PhD. At first, I met a friend who was doing here her PhD at Scripps and later her postdoc at UCSD. We met at Cold Spring Harbor Conference in China. So she told me all great things about San Diego. And then a person came to my lab who was a lab manager here at Salk, and then she told me all great things about Salk.
00;10;19;21 – 00;10;25;20
Aksinya
So I didn’t hesitate and applied right away and got so lucky that Nicola was interested.
00;10;25;23 – 00;10;40;19
伊莎贝拉
That’s so cool. You went from kind of general biology to the brain to neurodegeneration and DNA mechanisms and telomeres and synapses more and more specific as you went on until getting to Salk. What exactly are you studying now?
00;10;40;21 – 00;11;13;09
Aksinya
We are interested in the cells called astrocytes, which are star shaped glia cells, which are very important for central nervous system. And they play very important functions, such as providing trophic support to neurons. They regulate recycling of neurotransmitter, the molecule that neurons use to communicate to each other. They also form a part of blood brain barrier. This barrier that filters what ions and molecules can go from the blood inside the brain. And also astrocytes.
00;11;13;09 – 00;11;43;29
Aksinya
They release different molecules that can trigger synapse formation, and then they wrap around the synapse and regulate their stability and strength. Astrocyte, by releasing different molecules, can actually trigger the increase of a very different receptor at the synapse. So the regulation is very specific. And I’m working on one type of this molecules. Basically this molecule increase of a certain receptor which characterize a stable synapse.
00;11;43;29 – 00;12;16;17
Aksinya
And this molecule is actually regulate establishment of synaptic stability and development. Interestingly enough, in Alzheimer’s disease, these type of synapsis diminished. So we thought, great, we can get this knowledge from the development and apply to Alzheimer’s disease context. So what I do in my project, I overexpress these molecules in the astrocytes in the models of Alzheimer’s disease. Astrocytes secreted in the synapse increased number of that receptors and make synapsis stronger.
00;12;16;17 – 00;12;24;11
Aksinya
And I see if I can prevent or rescue synapse lost. And if this can have effect on memory and cognition as well.
00;12;24;14 – 00;12;29;25
伊莎贝拉
So are you looking at models of Alzheimer’s disease or are you just looking at aging models?
00;12;29;27 – 00;12;40;09
Aksinya
I’m working specifically with models on Alzheimer’s that also represent different hallmarks, such as tau tangles or amyloid plaques.
00;12;40;11 – 00;13;04;14
伊莎贝拉
Tau tangles and amyloid plaques are two different protein blockages that are characteristic of Alzheimer’s disease. Tau protein tangles tend to occur inside neurons, while amyloid protein plaques clump up between neurons.
00;13;04;17 – 00;13;19;11
伊莎贝拉
So in addition to looking at these hallmarks of Alzheimer’s, you’re also finding out a lot of things about synaptic strength and synaptic loss. Are those things that can be applied outside of Alzheimer’s to help understand the brain more generally, or how memory works?
00;13;19;14 – 00;13;45;10
Aksinya
This is definitely very important in translational research because, not only Alzheimer’s but other neurodegenerative diseases, they also experience synapse loss. So it can be applied to many conditions. The molecule that I’m using will be applied specifically where these types of receptors are lost. And yeah of course doing this research I learn all about memory.
00;13;45;10 – 00;13;52;13
Aksinya
How it forms, how it stabilizes, and how it’s lost in disease.
00;13;52;15 – 00;13;55;22
伊莎贝拉
What, to a neuroscientist, is memory?
00;13;55;22 – 00;14;11;24
Aksinya
So all of us, we have new experiences by visiting a place and meet new people. Right. So the memory is the ability to retain that information over time. And memory can be studied at different levels.
00;14;11;26 – 00;14;54;27
Aksinya
Psychology, anatomy, electrophysiology, and molecular biology. So me as a molecular biologist, I’m looking at the synapse, which is a key player in memory formation. So learning and memory is associated with activation in the brain upon experience. So neurons become activated. And then, using neurotransmitter, they transmit signal one to another. A neurotransmitter is released is bind to receptors on the next neuron. They open, allow the ions in, and cause all this molecular changes, which, in turn, can change the structure of the synapse and make it more stable and responsive.
00;14;54;27 – 00;15;09;09
Aksinya
Upon memory recall, in response to a specific such as smell, an image, or sound, this network that was reinforced will be activated. And when synapses are weakened or lost, it’s where the memory is affected.
00;15;09;11 – 00;15;25;25
Aksinya
And this can happen naturally, like when we are forgetting, or in disease when we don’t want to lose this memory. Unfortunately, all this pathological processes, they interrupt healthy synaptic function.
00;15;25;27 – 00;15;48;15
伊莎贝拉
So when you’re looking at this kind of stuff at Salk, is it helpful to have all these different disciplines working together, immunology, neuroscience, all these different backgrounds, even just in Nicola’s lab, not even considering other labs that you could be talking with members of that are your friends during lunch. Do you find that helpful when you’re approaching questions and doing the research?
00;15;48;17 – 00;16;12;29
Aksinya
Yeah, no, this is great because, in our lab, everybody has such a different expertise. We have immunologists, electrophysiologist. I’m a molecular biologist who came without any knowledge to neuroscience. So it’s very impactful to discuss all these things with each other. And on the lab meetings, somebody has more expertise with experiments on the memory, someone with the genetics.
00;16;12;29 – 00;16;21;10
Aksinya
So it’s very helpful. And we all collaborate together on each other’s project, try to get the best knowledge as we can.
00;16;21;13 – 00;16;33;06
伊莎贝拉
Yeah, yeah. It’s one of my favorite things about Salk because everyone seems to work together. It’s very, it’s very cool. And is there anything you’re working on right now that you’re really excited about currently?
00;16;33;06 – 00;17;09;10
Aksinya
I’m analyzing all this data on the effects that we have on the synapses. I’m also looking at the neurons and other glia cells, and as well as analyzing data from behavioral experiments where we seem to be seeing some encouraging effects. So I’m very excited about that. And in my last years of the postdoc I’m also trying to expand my tools and the models that I’m working in on looking at Alzheimer’s, not only in the models that I’m working right now, but also with human models.
00;17;09;10 – 00;17;39;00
Aksinya
I think it’s very powerful. And researchers have developed a lot of past years. I’m not working in the right now, but one of my biggest interests is, to look in Alzheimer’s in 3D human organoid cultures which resemble areas of the human brain. Right. And this is powerful not just because it’s just human cell, but also thinking that usually we use transgenic models which carry the familial mutation.
00;17;39;02 – 00;18;06;22
Aksinya
However, in humans, familial mutation account maybe only 4 or 5% of Alzheimer’s, whereas the rest 95 are sporadic cases. So taking human cells from a patient with sporadic cases, we can develop organoids and mimic some of that, model some of that pathology. I got lucky and got selected and last year I attended the Stanford Human Brain Organogenesis Workshop.
00;18;06;23 – 00;18;19;06
Aksinya
It was great hands on workshop where they taught us all the lab work and all the applications. I hope I can do a little bit of that research in here, and maybe start with some collaborations.
00;18;19;08 – 00;18;40;28
伊莎贝拉
And I think it’s cool to see basic research and medical research kind of moving in the same personalized direction, keeping those epigenetic markers, like you said, on these models, that’s a huge step. It’s very exciting.
00;18;41;01 – 00;19;11;01
Aksinya
I’m actually also really excited that in our project, we’re looking at really these early stages of disease progression, which is very important because earlier you can target the disease, maybe more chances of a successful outcome you can have. That was a great breakthrough with all these drugs that were approved by FDA that target amyloid. I think since Alzheimer’s is such a complex disease, it would be cool to combine those with drugs that target other aspects of the disease progression.
00;19;11;01 – 00;19;25;27
Aksinya
For example, accumulation of tau, which pathological tau can actually in many ways impair synaptic function, or combining it with approaches that I’m developing right now to increasing synaptic strength and combat the disease.
00;19;25;29 – 00;19;30;22
伊莎贝拉
Do you think the future of Alzheimer’s care is going to be preventative rather than reactive?
00;19;30;25 – 00;20;04;08
Aksinya
Well, since majority of the cases are sporadic, I think this may happen if we understand all the genetics and all the risk and protective factor, then maybe we can have a better prediction which people are at risk.
00;20;04;11 – 00;20;07;16
伊莎贝拉
So what are your plans next after Salk?
00;20;07;16 – 00;20;45;04
Aksinya
So since I’m in the last year of my postdoc, I’m trying to get the best knowledge I can and develop my skills as much as I can. And I’m really interesting in continuing my career as a researcher. I will try to, I guess, apply as a PI, for an academic position this upcoming year. Honestly, I’m quite open to work in the academic setting or more industrial or biotech because my interest is really keep working on memories, Alzheimer’s, translational research.
00;20;45;04 – 00;20;58;27
Aksinya
So I think I can benefit in both. But I guess the first choice will be in academia because I like how it allows you to be creative as a scientist, and I honestly, I’ve never been in on the other side, so I don’t know.
00;20;59;04 – 00;21;06;01
伊莎贝拉
Do you ever think about teaching or what you would want to teach if you were to be in an academic setting and in a classroom?
00;21;06;05 – 00;21;39;15
Aksinya
Honestly, I have never had the experience teaching in the class, so I don’t know if honestly, I’d love it or not. I don’t know if you can tell. I fear public, but actually I honestly enjoy working with people one on one. And this is another great thing about Salk that we have students that are coming, undergrad students that are coming from UCSD, and I had a chance to work with many undergrads, and I really enjoy teaching them and passing them my knowledge and my expertise.
00;21;39;17 – 00;21;41;29
Aksinya
So maybe.
00;21;42;01 – 00;21;47;21
伊莎贝拉
And what kind of stuff do you get up to off campus? What’s life like for you in San Diego?
00;21;47;24 – 00;22;22;21
Aksinya
Well, there is a whole another life. Well, I like, do many different things. One of the biggest thing I’m into, I’m an, I’ll call it, semiprofessional dancer. I started to dance ballet when I was at school. And then at the university I danced urban dance style like a hip hop and funky styles and breaking, which I still do. But then during my PhD times, I got involved in the Latin dance, salsa and bachata.
00;22;22;21 – 00;22;51;17
Aksinya
And I grew a lot in that world. And at some point I started to teach class with my former dance couple, which was a PhD student from another lab across. So currently I’m not teaching, but I’m in two dance companies. And actually I have four shows this weekend. And then one is today.
00;22;51;18 — 00;22;51;20
伊莎贝拉
Four? That’s crazy!
00;22;51;21 – 00;22;52;27
Aksinya
So I’m currently like working on developing myself as a dancer. In my free time, of course.
00;22;53;02 – 00;22;57;20
伊莎贝拉
That’s great. You are you hoping to keep that up, are you going to keep dancing?
00;22;57;23 – 00;23;35;00
Aksinya
I think so. I really enjoy it. And I think, it helps me actually be better scientist because both fields are very creative, but also require a lot of mind work, then it’s nice to have a balance between sedentary lifestyle. Then it also helps me in these things, like a public performance. And also, I think an interesting aspect for me is that, you know, sometimes a hard experiment didn’t work or something when it’s so I always have that other side that makes me happy.
00;23;35;00 – 00;23;45;01
Aksinya
And when sometimes I don’t do a good performance, I have my experiments I’m so excited about. So, it’s kind of helped me to feel good level of happiness.
00;23;45;01 – 00;23;51;10
伊莎贝拉
Well, that is a beautiful note to leave things on. Staying happy, feeling good. Thank you so much for being on the podcast.
00;23;51;12 – 00;24;01;24
Aksinya
Thanks for having me. My pleasure.
00;24;01;26 – 00;24;32;14
伊莎贝拉
Aksinya is such a fantastic example of what makes Salk science special, especially when it comes to Alzheimer’s. And that’s the combination of interdisciplinary collaboration and basic research. Interdisciplinary collaboration creates a give and take and push and pull of information that shapes questions only Salk scientists can ask. And these one of a kind questions mean one of a kind answers, bringing us closer to understanding how our brains age and what disease progression and prevention may look like.
00;24;32;17 – 00;24;56;07
伊莎贝拉
Basic research means we aren’t just enhancing what we know about a single disease or disorder. Aksinya is going back to the basics, looking at synaptic dysfunction that impacts all of us as we age. The further she digs, the more we know about how the brain works for everyone, how memories come and go, how our brains change over time, and how we might prevent these general functional losses.
00;24;56;10 – 00;25;13;24
伊莎贝拉
The success of this collaborative, basic research relies on scientists that are as friendly as they are talented. Speaking with Aksinya was a tremendous reminder of that, and I’m excited to see what she discovers next.
00;25;13;27 – 00;25;44;11
维多利亚之声
Beyond Lab Walls 是萨尔克传播办公室制作的一档节目。收听萨尔克最新科学故事，请订阅我们的播客，并访问 Salk.edu 加入我们新推出的独家媒体频道 Salk Streaming。在那里，您将看到我们的科学家访谈、近期研究视频以及世界知名教授的公开讲座。您还可以浏览我们屡获殊荣的杂志 Inside Salk，并订阅我们的月度通讯，及时了解这些围墙内的世界。.