SciPodChat

S01-E01: Autophagy-The Science Behind Cellular Self-Cleaning & Intermittent Fasting [Part-1]

• Dr Biswajit Podder • Season 1 • Episode 1

Share episode


Join us on SciPodChat, hosted by Dr. Biswajit Podder, featuring guest Dr. George Chiduza, as we delve into the cutting-edge of molecular biophysics and autophagy. This episode explores the intricate world of autophagy, structural biology, and electron microscopy, shedding light on how intermittent fasting might activate this cellular self-cleaning process. While this discussion focuses on the fundamentals and advancements in autophagy, understanding this process provides a foundation for discussing broader topics in future episodes, including optimal fasting times, weight loss, health benefits, popular intermittent fasting methods like 16/8, and its implications for conditions like diabetes and various diets. Dr. Chiduza shares his journey from Zimbabwe to becoming a leading researcher in molecular biology, illuminating the critical link between DNA, protein structure, and autophagy in intermittent fasting. Dive into the conversation to learn how autophagy modulation is at the forefront of treating neurodegenerative diseases like Parkinson's and Alzheimer's diseases. This show is an excellent resource for science fans and professionals, and it looks like it will help people understand complicated scientific ideas and useful health information.


This episode is supported by  STEMdorado

Snapshot of Intermittent Fasting

Intermittent Fasting (IF) combined with the power of autophagy. This guide is your key to understanding how these two concepts can lead to significant weight loss.  From rejuvenating your immune system to enhancing brain health, let's explore how to harness these processes for your well-being.

What is Intermittent Fasting?

Intermittent Fasting isn't just a diet trend; it's a lifestyle change that alternates between periods of eating and fasting. This pattern isn't about changing what you eat but rather when you eat. By strategically timing your meals, you enable your body to enter periods of fasting, where the magic of autophagy can work effectively.

Understanding Autophagy

Autophagy, meaning "self-eating," is a natural process where your body cleans out damaged cells to regenerate newer, healthier ones.


The Benefits of Intermittent Fasting and Autophagy

  • Renewed Immune System: Fasting regenerates immune cells, enhancing your body's defense mechanisms.
  • Neurological Improvements: Promotes growth of new brain cells, improving memory, focus, and cognitive function.
  • Mood and Mental Clarity: Enhanced brain function leads to better mood and concentration.
  • Reduced Inflammation: IF helps decrease inflammation, a known trigger for many chronic conditions.

Effective Tips for Intermittent Fasting 

  1. Ease into One Meal a Day: Gradually shift from two meals to one, increasing your fasting window.
  2. Combine with Healthy Keto: Enhance fat burning and energy levels by adopting a ketogenic diet alongside IF.
  3. Be Consistent: Track progress with photos and stay the course for visible results.
  4. Incorporate HIIT: Accelerate weight loss and health benefits with high-intensity interval training.

Simplifying Fasting for Everyone
To make fasting more approachable, focus on changing unhealthy dietary components like harmful oils, processed carbs, and toxic ingredients. Remember, fasting should be as natural as sleeping, aimed at healing and rejuvenating your body.


Conclusion
Integrating intermittent fasting and autophagy into your lifestyle isn't just about losing weight—it's about embracing a healthier, more mindful way of living. 

We Talk Science

Dr Biswajit Podder:

Hello, science Lover. Happy New Year. I hope you had a great break. Welcome to C, a podcast where we explain science puzzles in a way that everybody understands. This podcast is bought to you by Stam Durado. Stam Durado is owned by scientists and run by scientists. The goal of Stam Durado is to make learning fun and interesting for kids. The games and exercises on Stam Durado are fun and help kids study math and science at the same time. I am your host, dr Bishrit Puddar, and today we are delving into the fascinating world of autophagy With our special guest, dr George Chiduja, a scientist in molecular biophysics and autophagy. He got his PhD in molecular biophysics with focus in structural biology. Welcome, george. Can you explain a bit about biophysics and structural biology for our audience, please?

Dr George Chiduza:

So, first of all, thank you for inviting me to talk about my work and to talk about science in general. So biophysics is a contraction of biology and physics, so it's the application of physical techniques and physical principles to biological systems. So the different way of putting it is, when it comes to the sciences, the divisions that we have between the different subjects are there to allow us to treat the world in different ways, but these divisions are divisions that we create. So there are actually no true separations between biology and physics, and in biophysics we combine the two in a sense.

Dr Biswajit Podder:

Thank you for my audience, george, could you tell us about your journey into molecular biophysics and autophagy and what is your inspiration to focus on this research? So why are you interested on that? So can you tell me a bit more?

Dr George Chiduza:

Sure, so my journey starts in Zimbabwe, where I was born and raised, and I did so. I've always had an interest in science in general, and I decided at the end of high school that I was going to study molecular biology in university, and the reason for that was I wanted to do something that was interesting to me but also had a social value, and what I had in mind was learning how to modify crops to make them drug resistant, because that's important to an economy like Zimbabwe.

Dr George Chiduza:

So, in order to do that sort of thing, you need to understand molecular biology. Now, what I learned during the course of studying molecular biology was that so this may be familiar to some of your listeners, but all biological organisms have a blueprint or a set of instructions from which they can be constructed. That's usually contained in DNA, and molecular biology is the study of how the information contained in DNA is then converted into what we see in the organism. So why is it that some people have dark, curly hair and some people have straight, blonde hair? The process in which we go from the information in DNA to the physical traits is what molecular biology studies. Now, during the course of that study, I realized that a major limitation of our understanding of molecular biology was the relationship between DNA and protein structure.

Dr Biswajit Podder:

Right, absolutely.

Dr George Chiduza:

Now the. So you asked me at the beginning what structural biology is.

Dr Biswajit Podder:

Yeah.

Dr George Chiduza:

It relates to that question. So, if you, if you, I'm going to ask you a quick question. Yeah, what, like what would you say, is the difference between a fork and a knife?

Dr Biswajit Podder:

Okay, so you use knife to cut meat and and you use the pork to hold it right.

Dr George Chiduza:

Okay, so they have. They have different functions, but both of them can be made of the same material.

Dr Biswajit Podder:

Yeah, but they work both together right, so they work together, they can both.

Dr George Chiduza:

They can both be made of the same material. But what is it that makes the function of the knife different to the function of the fork? So it's not the material. There must be something else right, which is the knife has a sharp edge, whereas the fork has prongs in it. So it's so.

Dr George Chiduza:

To put it generally, it's the shape of the material that determines the different functions of the fork and the knife Right and shape, we can also call structure. Now, proteins, in a similar way, can be made of the same same material, right, but when they but because they adopt different shapes, they have different functions. So the proteins that allow you to see in the retina of your eye are made of the same material that makes up the proteins that make up your hair, for example.

Dr Biswajit Podder:

Right.

Dr George Chiduza:

But they have different functions because they have different shapes. And my job, as you can imagine, it's difficult to see the shape of proteins. Proteins are very, very small.

Dr Biswajit Podder:

Yeah.

Dr George Chiduza:

So we're looking, we're talking about scales round about tens of billions of a meter Right, so it's like very, very small.

Dr Biswajit Podder:

So so okay, if you bring the discussion that we cannot see the protein structure in naked eye. So how do you see the protein in in the laboratory? So can you tell them to our audience, the how do you see the protein? You know, as I'm also a scientist. So oftenly my non scientist friend asked me oh, protein is small, or DNA small and DNA small. So how do you see them? So what kind of technique do you use to see the proteins in the laboratory?

Dr George Chiduza:

That's a, that's a very good question, and so with most small things we can see them by using some kind of magnification. So for small, small organisms, creatures, you can see maybe with a magnifying glass If you're looking at cells. Hopefully, members of our audience have had an opportunity to use something like a light microscope where you can put maybe a bit of onion or brush off some pollen from a flower and which by eye you can't see. But using the microscope you can see.

Dr George Chiduza:

And in the same way, we use a different kind of microscope, the electron microscope, to visualize some of these small molecular structures.

Dr Biswajit Podder:

So what is electron microscope? What is the difference between normal microscope we often see and then what electron microscope you used in your research? Can you explain a bit how they are different yet?

Dr George Chiduza:

Yeah, so hopefully, in what I've just previously said, your audience can appreciate that microscopy is microscopy. The difference is one is light microscopy. That's what we're used to, and what that means is we're using light in order to see the objects that we want to look at, whereas with the electron microscope we're using electrons. So electrons are constituents of atoms, so small particles which we can use to see small molecules.

Dr Biswajit Podder:

Right, okay. So thank you so much for your explanations about biophysics, structural biology and two different kinds of microscope. So my next question why you are interested in biophysics in your PhD in Liverpool, yeah, so what is your project? Was there actually? And then afterwards you moved to Francis Crick Institute, right, so as a postdoc. So what is your motivation to move to Francis Crick Institute and working on autophagy? So can you explain a bit?

Dr George Chiduza:

Yeah, sure. So, like I mentioned, I was interested in basically modifying the genetic material of organisms and how that's related to proteins. Is that genes contain instructions that make proteins. And I realized that even though we knew what the genes were, or it was easy to work out what the genes were, it was difficult to know what the shapes of the proteins were. Yeah, because, remember again, the shape is what determines the function. In the same way it determines distinguishes a fork from a knife, right. So when I realized that that was a major gap in our understanding in science, I decided I would pursue my PhD in techniques for understanding that, electron microscopy being the main technique, a particular flavor of electron microscopy called cryo electron microscopy. So the cryo just means we're working at very cold temperatures, so this is liquid nitrogen temperatures.

Dr Biswajit Podder:

Why is it important that low temperature? So can you explain a bit? Why is cryo temperature needed?

Dr George Chiduza:

Yeah, sure. So when we say very low temperatures, just to give you an idea, in most rooms in, let's say, here in the UK, the temperature is between 20 to 22 degrees Celsius.

Dr Biswajit Podder:

Okay, it depends on which weather. Oh, of course.

Dr George Chiduza:

True, but roughly. That's what we would consider room temperature.

Dr Biswajit Podder:

Right, I'm just kidding yeah.

Dr George Chiduza:

So just to give you an idea so liquid nitrogen temperatures minus 165. So it's quite cold. So why do we work at these temperatures? So electrons are. If we were to release an electron in the air, it would quickly be absorbed by the air, so we couldn't use it for forming images. In the same way, if I were to put an opaque piece of paper, or a piece of well, any piece of paper in front of the light source, of light microscope, I wouldn't be able to see an image. So for electron microscopy we work in a vacuum. So we remove all the air molecules inside the instrument and the electrons can then pass freely. However, there's a phrase which my chemistry teacher always liked to use, that nature abores a vacuum, and essentially what that means is if you create a vacuum, by removing all the air molecules.

Dr George Chiduza:

What happens is something will try and take the place of that vacuum.

Dr Biswajit Podder:

Right.

Dr George Chiduza:

And in our case we're putting a sample the thing we want to image into the microscope. So if we're not careful, that thing can basically be destroyed by the vacuum, right? But if we work at cold temperatures that doesn't happen. That's one of the reasons, among many others, but we won't get into the other reasons now.

Dr Biswajit Podder:

Right, so basically so our next discussion, as I mentioned, that, like most of the audience is interested about probably autophysics, because in social media there's a lot of people discussing about the intermediate fastings and then they know the science behind that, like autophysics, and even someone got Nobel Prize for autophysics research and over the last decade a lot of advancement happening in autophysics research. So can you explain what is autophysics and why it is essential for our body or our health?

Dr George Chiduza:

Yeah, thanks for that question, Dr Pote. Thanks, dr Pote. Essentially, with the technique up in describing, you can work on a variety of questions. And one of the questions that I ended up working on was autophagy and, like you've mentioned, it's quite a topical subject. So what is autophagy? So the word comes from two terms auto, meaning self, and phagey, meaning to eat. So essentially, if you put together that expanded version of the word, it means to eat oneself.

Dr Biswajit Podder:

So you mean that in our body is happening that, like our cells are engulfed by another cells, or what do you mean by eating? Can you explain a bit more?

Dr George Chiduza:

Yeah, and that's a key question, because there is a process where cells eat other cells, but that's called phagocytosis.

Dr Biswajit Podder:

Yeah, so most of my non-scientists friends know about it, so they ask me that questions.

Dr George Chiduza:

But yeah, so, however, this is different to phagocytosis. This is happening inside a single cell. Actually, we think that this process happens in all the cells in your body. You have formation of a small bit of membrane.

Dr Biswajit Podder:

What is membrane actually?

Dr George Chiduza:

So it's somewhat straightforward. So we've most of us have seen something that looks like a membrane, so try putting a bit of oil on water. The oil separates from the water. Now, membranes are composed of lipids the same things that make up oil, and because lipids don't like water and they separate from water the boundaries of our cells and the boundaries of the small factories that we call organelles. So these are things like the mitochondria, for example, which the audience might know, that provide energy to all of those.

Dr Biswajit Podder:

To our body.

Dr George Chiduza:

Yeah, so all of these are bounded or contained within these fatty molecules. And these fatty molecules, because they don't like water, they form boundaries or membranes as we refer to them. So, going back to the explanation of what autophagy is so essentially in each cell or, for the sake of simplicity, imagine in a single cell you have a formation of such a membrane where there was none before, and that membrane then encloses or captures something inside the cell.

Dr George Chiduza:

And then it delivers it to another one of these little factories inside the cell, one of these organelles called the lysosome. And the lysosome contains enzymes, which are proteins whose function it is to break apart the different components that make up cells. So cells are made up of these fatty molecules, like I've mentioned, lipids. They're made up of DNA, which I've already mentioned, and that can be broken up into what are called nucleic acids. You also have proteins themselves, which can be broken up into amino acids, and essentially the process of autophagy is going from that encapsulation of material and its delivery to this lysosome organelle for degradation, right. So it happens all the time in your body, continuously.

Dr Biswajit Podder:

And why it is important if it happens all the time in your body. So at a very limited level it is happening all the time.

Dr George Chiduza:

So you can imagine the cell. The structures in the cell can become damaged, for example, so they need to be removed.

Dr Biswajit Podder:

But the cell is very clever.

Dr George Chiduza:

It recycles the material. So it's very important to have a good understanding of the cell. So let's say, mitochondria have become damaged, they need to be removed. The cell encapsulates it.

Dr George Chiduza:

Mm-hmm inside this membrane, the, the autophagosome as we call it, delivers that mitochondria to the lysosome and then the, the lipids that make it up, the nucleic acids and the amino acids are then released. Yeah, now what the cell can then do is it can make new mitochondria, for example, or new structures, even and this is particularly relevant in situations where, where autophagy is induced. So what do we mean by induced? And this goes back to your question about, you know, conversations around intimate, intimate and fasting, yeah, and so on.

Dr George Chiduza:

So in conditions of stress, like Situations where you're fasting, mm-hmm, your cell, the cells, no longer have Access to materials that they need to build themselves or to make these structures and what they do in responses. They can break down existing structures and then use the raw materials, the amino acids, new clay, cast, its lipids To create new structures that allow them to respond to the news, to whatever stress it is. So nutrient starvation is a common stress that we look at, but there can be other stresses. For example, you can have a, for example, for cells infected by another, by bacteria or by a virus. The cell can use this mechanism essentially to remove these bacteria or these viruses and, by and in this process, the raw materials released Can be used to make things like antibodies, for example, which cells can use to to respond to To the invading virus or bacteria. So going back to intermittent fasting and autophagy, so obviously if you fast, nutrient starvation or fasting induces autophagy and, interestingly, autophagy has been linked to lifespan extension. So people tend to, at least in, at least in worms.

Dr Biswajit Podder:

Okay, so what do you mean? So it's very interesting.

Dr George Chiduza:

So scientists, you can imagine we don't always do experiments on people. We can't staff people on purpose.

Dr Biswajit Podder:

Actually we don't do it. We don't do experiment on human body. Initially right.

Dr George Chiduza:

Oh yeah, we always start with Simpler model systems, as we call them, simpler systems, non-living or animal models right, appropriate.

Dr Biswajit Podder:

Okay, back to your interesting like point to warm. So what is that?

Dr George Chiduza:

Yeah, so and so, with its intermittent fasting, there are several benefits that come with it. So one of them is improved Regulation of insulin signaling, for example, so that can help, like with kind of avoiding diabetes. You have cognitive effects. That means you have effects on on the mind itself. So it's been shown that when you and, by the way, intermittent fasting means you go for maybe 16 to 18 hours.

Dr Biswajit Podder:

So yeah, I'm between meals. Yeah, because intermittent fasting the idea is to starve your body for certain period, so the ideally it considered like 12 hours to 20 hours so you can starve all the time and then you can eat Any kind of food for like few few hours or several hours. So there's research. They found that like mostly 16 hours is the ideal for intermittent fastings and they have seen the bet that like best outcome of intermittent fasting.

Dr George Chiduza:

Yeah, yeah, so, yeah, so, yeah. So some of the reasons to do it, like I mentioned, better, better Insulin signaling, which helps with controlling sugar levels in your bra, in your blood. Cognitive benefits as well. So you have. So it's been shown that when you fast intermittently, there's a Hormone or signaling molecule that's released in your brain that controls the, the growth of neurons, for example. So there are many benefits to intermittent fasting, one of them being that it induces autophagy, which allows for clearing of damaged or damaged structures in your, in your cells, and Also could potentially help with weight loss.

Dr Biswajit Podder:

So what do you mean? I understand that, like Intermittent fasting is Scientifically proven method, isn't it?

Dr George Chiduza:

I Think there have been trials in humans, at least for intermittent fasting right, Okay cool.

Dr Biswajit Podder:

So let's say like, as I understand that autophagy is really required for our body, homostasis, right to maintain our normal body conditions, right? So what happened? Let's say like, somehow the process is disrupted, and if it happens, so what could be the consequence for our body?

Dr George Chiduza:

Yeah, very good question, and this is, I must say, this is an area of active study, but there is there is some thinking that If you have impaired or reduced autophagy, this can lead to things like neurodegenerative diseases. It can also lead to Situations where so for so I've already mentioned the clearance of mitochondria. So when mitochondria become damaged, sometimes they can produce these reactive oxygen species. So these are just derivatives of oxygen that have the potential to damage other structures within the cell and this can lead to damage of DNA, which can contribute to the development of cancer. This can lead to damage of other structures in the cell, which we think might accelerate the aging process In terms of neurodegenerative disease. So a lot of these diseases involve accumulation of these essentially clumps of protein, and by neurodegenerative disease we're talking about things like Alzheimer's disease, parkinson's disease, and autophagy is thought to be involved in the clearance of the early forms of these clumps.

Dr Biswajit Podder:

So basically, as you mentioned, that, like Otowasi, had a lot of implications on neurodegenerative diseases. So do you know, do you have any update, or do you know that any kind of like breakthrough research is ongoing on to treat those kinds of neurodegenerative diseases?

Dr George Chiduza:

I wouldn't say breakthrough, but there is because we have this understanding. There are companies that are looking into developing small molecules, essentially drugs that you can take in the form of pills that would stimulate autophagy.

Dr Biswajit Podder:

As you know that when I was working also Francis Crickin's stage with you in the same lab, so I also worked on to find out new molecules. Like we used to focus on autophagy, so do you think that this kind of research also ongoing on degenerative diseases, to find out new molecules to treat like Alzheimer's disease or Parkinson's disease?

Dr George Chiduza:

Yeah, so I know at least one company, but-.

Dr Biswajit Podder:

I think it's better not to mention that.

Dr George Chiduza:

Yeah, I won't mention any names, but I know at least one company that's working on finding molecules that increase autophagy. But there are situations where maybe autophagy, maybe you might want to reduce autophagy, right? So this is in the context of things like cancer.

Dr George Chiduza:

So, sometimes cancers can exploit autophagy to divert nutrients into their uncontrolled growth. So in that case you might want to inhibit autophagy, and that's the scenario we were looking at and are more in your research than mine. But your research was based on some work that I'd done on proteins involved in the process.

Dr Biswajit Podder:

Yeah at his in nine and two. A yeah yeah.

Dr George Chiduza:

And the idea was. So. What we discovered was that these, like Dr Potter mentioned earlier proteins can work. Even though they may have different shapes and different functions, they often have to work together. And these two proteins I managed to show with others that these two proteins need to work together closely I think we will discuss more about in our next episode about your research.

Dr Biswajit Podder:

Yeah, so probably our audience will be more interested to deep dive into your research. So let's keep in the for next episode. So basically, there's a lot of research on going on autophagy nowadays. So what do you think in the next 10 years, how the field will be evolve in autophagy fields? Do you have any kind of what direction. The research will be happening or yeah.

Dr George Chiduza:

So there's different levels where research is taking place. So there is the basic, what we call basic research or basic science, and the purpose of basic research or science is to understand, simply to understand how things are working in normal, healthy conditions and how things are not working in disease, and within that area there's still a lot to understand. We don't know all the details of how autophagosomes form. There is some evidence that different cells or different organs in your body the liver, the heart, muscles, they might be carrying out autophagy in slightly different ways, right, so there should be, hopefully within the next 10 years there'll be progress made in understanding how autophagy is happening in more detail generally and in more detail in organ or tissue specific context, and as often as the case in biology, there may be sex differences as well. So essentially it's understanding what's happening in autophagy generally. So in basic research, the other line of research is translational or applied research.

Dr Biswajit Podder:

Right.

Dr George Chiduza:

And we've already touched on some of the directions that this is heading toward, and this can be generally divided into sort of finding ways of controlling autophagy in a way so as to increase it, which might be desirable in conditions like early neurodegenerative disease, or looking at ways of reducing or inhibiting autophagy, which might be useful in conditions like cancer. So I mean, it's very difficult to predict the future, but based on my knowledge and experience, those are the areas that I see research going.

Dr Biswajit Podder:

So in the next episode we will talk more about George's work on autophagy. He's going to talk about autophagy proteins called ATG9A, 9B and ATG2A. We will delve deeper into the topic in our next episode To our listeners. Thank you for joining me on C. Let's know science together. Until next time, stay curious, stay inspired, stay tuned for more exciting conversation right here on your favorite C. Take care, bye-bye. I'll see you next time. I'll see you next time.