2023-01-18 by Khushi Goel

[Transcript] IndiaAsksWhy | Why Do We Have Moles and Birthmarks?

[00:10] Both- “Hi Everyone”

U- I am Utsuka

J- I am Jigyasa

Both- And you are listening to IndiaAsksWhy.

U- A science podcast supported by IndiaBioScience

J: Where we do the research for you to get smarter.

U: Join us, as India becomes more curious,

Both: one question at a time!

[00:34] Utsuka and Jigyasa are always curious observers! We all know that. Now they also have curious friends! One of their friends: Rhythem Goel has asked them “Why do we have birthmarks and moles?” So Let's see what the curious team found out.

In the interview segment, they talk with Dr. Ramray Bhat, a cancer scientist from the Indian Institute of Science (IISc), Bangalore. He tells them why cells sometimes behave abnormally to give rise to moles and birthmarks and what causes some cells in our body to become cancerous.

[01:25] U: Do you have any birthmarks and moles, Jigyasa?

J: Yes, I have one dark spot on my neck, what about you?

U: I had one when I was a baby, but my family says it eventually disappeared!

J: How curious! Birthmarks and moles are definitely mysterious. Looks like the cause of birthmarks and moles has puzzled the scientists too! There doesn’t seem to be a defined reason for such a thing to happen, but from many years of research, the scientific community has speculated several reasons!

[02:00] U: Woahhh..but before getting there. What exactly are birthmarks and moles?

[02:10] J: Ah yes! Let's define them: A birthmark is any mark on the skin right from birth- not so difficult! These can be any kind of mark- some are reddish or raised- giving a strawberry-like appearance, some are a bit brownish- giving a coffee-like color on the skin, and some can be very dark. There is a wide variety in the types of birthmarks we can have!

U: okay okay.. that's a lot of types of birthmarks! And what about moles?

[02:46] J: Yes! A mole is a type of skin growth where the pigment cells in the skin tend to form a cluster. They can appear on the skin or the mucous membranes- like inside the mouth!

U: formed from a cluster of pigment-producing cells? Let me guess, you are talking about melanocytes?

J: Yes Utsuka! You remembered we had discussed these are specialized cells that give color to our skin!

[03:19] U: Exactly, but my question is, why do these melanocytes form clusters?

J: That’s a very interesting question. One group of doctors thinks that this could be because the cells have lost the ability to hold each other to keep a flat shape or surface.

U: What does that mean?

J: Cells usually stay in a flat stretched shape, like a rubber band. But when the cells lose the molecular bridges which keep them flat, they cluster together like a released rubber band.

[03:57] U: Oh that explains why some moles pop up from the skin surface. But Jigyasa, not all marks we have on our skin are raised. As you said, some birthmarks are just darker-colored marks on the skin, why does that happen?

[04:20] J: Utsuka, you have yet another interesting question! However, we need a clear answer to this. As I mentioned before, we only know of some speculative reasons. And for these reasons, we need to go back in time, to when we are still just a ball of cells!

[04:39] U: Ball of cells? Do you mean when we were embryos?

J: Yes Utsuka, looks like you are paying close attention to all our discussions! I was, in fact, hinting at embryos. As embryos grow, cells within them start to specialize and give rise to different kinds of cells. One such type of specialized cell also gives rise to future melanocytes. These melanocytes are supposed to station themselves in specific layers of cells in the embryo. When this stationing happens correctly, we land up getting our normal skin with the standard melanocytes.

[05:34] U: So what happens when they aren’t stationed properly?

J: Recent studies have found that those melanocytes which have taken a different route develop differently from the rest of our melanocytes. And, this differential development could then become a cause for some of the colored birthmarks that we see in children.

U: Ah, I see!

[05:49] J: But, some of the other types of birthmarks may have a less severe reason too. They may be simply formed because the melanocytes decided to produce more pigment in a certain spot, instead of increasing their numbers.

U: That's a lot of reasons! Why do these melanocytes decide to behave differently all of a sudden?

J: I was hoping you would ask this question, haha! This could happen due to mutations in melanocytes, which affect the production of the pigment! Do you remember what were mutations Utsuka?

U: changes in the genes of the cells?

J: Exactly!

[06:27] U: In all the causes of the moles and birthmarks you described, it looks like there was something up with the cells. They were either growing too much or growing in abnormal directions, or growing on top of each other. I wonder why cells start to behave like this suddenly.

J: I think I know the perfect person to answer your questions! Lets ask Dr. Ramray Bhat.

[06:55] J: And now… It’s time to ask a scientist.

[07:00] U: So welcome back everybody. So we now have Dr. Ramray Bhat who is a cancer researcher from the Indian Institute of Sciences, Bangalore. He studies how cells become cancerous. So he does a lot of experiments with actual tissues but also uses computer software to decode how cells behave. With that, Jigyasa I think we can go ahead and ask our questions, shall we?

[07:23] J: So Dr. Ramray why do cells all of a sudden become abnormal?

[07:32] R: Okay! So this leads one to think about what is normal for a cell and what is abnormal for a cell to be in. and one needs to understand that normal and abnormal for a cell can be looked at not just at the level of the cell but more in terms of its relations with its surroundings. What makes cells normal is when the relationship of these cells with their other neighboring cells and their extracellular matrix is normal. When they can speak to each other and communicate with each other through signals - chemical, physical, and so on. And then decide okay together we are in a state where we are able to function and therefore we are necessarily supposed to do two things - one is move and two is divide. Okay? So in healthy organs and healthy tissues therefore what you have is that the organ or tissue remains stable by which I mean the cells of that organ or the tissue don’t go wandering around, don’t start dividing either. Over time, these relationships between the surroundings and the cells can be altered due to various reasons. These reasons could be, for instance, risk factors that come in through the environment. You mentioned things that happen on the surface of the skin such as Ultraviolet radiation, injuries, and things like that. Food habit risks, aging, smoking, and so many risk factors we are exposed to. Stress in our lives and so on. All of these confounding agents basically start disturbing the relationship between the cells and their surroundings. And ultimately when those relationships through those communications are disturbed, that’s when the state moves from don’t divide, don’t move to either divide or move or both depending on the extent of that miscommunication or lack of communication.

[09:42] U: So how do you actually study such relationships between the cell and the environment and what causes it to change?

[09:52] R: Okay, so there are various ways by which you can study this. Again, experimental cell biology and experimental tissue biology use various models or various systems to study this. We for instance try to take the extracellular matrix that I talked about, and other cells - the normal cells, and cancerous cells, put them together. It’s like almost doing lego. We can put together whatever we want to under a microscope and then try to study, does the cell divide? Does the cell move? Or does the cell remain stable? And we see that in a lot of cases for example, when we take normal cells and when we put them in the normal environment, the cells remain healthy. However, if we take normal cells, non-cancerous cells but put them in an environment that is not typical to them, which is not what they would see inside the body when they are inside an animal or inside us, they would actually start dividing and growing. So it tells you that in a lot of cases what is normal and not normal is therefore guided by the environment in which you are in. alright? So what we study in our laboratory or most of us study I am talking on behalf of the community, we study cancer cells from both humans and animals which act as good model systems, we believe act as good model systems for the cancers we get. For example, mice are used as a model system because in many mice we do get the kind of cancer that we also see in humans so mice have also been studied and ‘murine’ cells from mice have been studied to look at how cancer is developed, and so on. So that requires us to actually go to patients, make cohorts of patients, take their cells and that’s the reason why. Yes, we do take cells from biopsies and so on.

[12:10] J: I am sure that there is certain kind of advanced microscopes that you must be using so maybe you can tell us what kind of microscopes these are and what kind of details you get to see with these microscopes?

[12:21] R: Some microscopes allow us to look at an entire tumor. So if I am interested in looking at a population of cells and how a population of cells behaves, I use microscopes that give me a more zoomed-out view. On the other hand, if I want to look at the mitochondria inside the cell of cancer which is present in the middle of a bunch of cells, then I would want a microscope that focuses me there at a very high resolution so I need say an extremely high-resolution confocal microscope or photon microscope. I can use another microscopy to actually not even see. So you know most microscopes see, but some microscopes feel. We use atomic force microscopy for instance to feel a tumor rather than see a tumor.

[13:06] U: I realized that you were also a clinician before becoming a developmental biologist and are now a cancer biologist studying the development of cancer. So we were curious to know about the transitions you made, a couple of them.

[13:20] R: When I did enter a very good medical school in Calcutta, I was adjoined in my first year when I was introduced to topics like anatomy, biochemistry, physiology, and so on. But as time went by, I realized I was in sort of a dilemma, as I moved more and more into medical school, I was stuck in dilemma as to does the, whether the disease occurs, how the disease occurs, and how the disease spreads or you know takes place was that more interesting to me or was it more interesting for me to know now that I know that it has happened, how can I diagnose it and how can I cure it which is a more interesting question. I was more interested in the more fundamental questions so I very quickly realized that I have to sacrifice one if I have to pursue the other. I was actually studying limb pattern formation using chickens as a model so that’s one of the classical models of studying limbs development so that was what I did for my Ph.D. and it had a lot of very interesting dimensions of both evolutionary biology and how developmental mechanisms evolve and as well as physics, how physics of form plays a very deep role in guiding the shape and size of organs and tissues then it was as un-medical a problem as possible.

[14:57] J: Did you like face challenges pertaining to this kind of interdisciplinary jump where you had to combine a lot of physics may be and a lot of physical phenomena to study a biological question?

[15:10] R: No so yes and no. So there are a couple of angles, one is of course one needs to have a really broad outlook towards it for being able to embrace it. But I realized very quickly that it is not possible for me to do everything together. So then again the second aspect being one has to embrace the aspect to have collaborators. In my post-doctoral lab, it was even more fantastic and it was a very big group where there were engineers as part of the students, I mean the post-doctoral group consisted of biophysicists, biochemists, engineers, and computer scientists. So everybody was tackling breast cancer together using their own different strengths and so on. Sp again conversations even among students would be intensely stimulating so all of that has been very important. Even coming here, even in IISc, you know we work with condensed matter physicists, we work with nanoparticle physicists. I have worked with engineers, microfluidic engineers, and none of that stuff can ever be done in my laboratory using my knowledge

[16:17] U: Let’s say some of our listeners wants to become doctors, engineers, and so on but they have that mind full of curios questions that they want to explore down the line so despite their background how can they sort of chase a curious question and add to the body of knowledge hence mean going on and related to that concept and topic.

[16:38] R: Right, I think the best way is to talk. It is very important to talk to as many people and as I said sometimes when I have questions that I know I cannot answer for instance, I have gone to many people, and many times I haven’t gotten the kind of responses I wanted. But it all depends on how curious you really are and how the question bothers you at 2 AM at night. And if it does, then you keep chasing and chasing and chasing people whom you feel may be the right source of person to help you with. So as long as one is faithful towards one’s zeal to solve the problem, I think it works out well.

[17:20] J: Do you now understand why we have birthmarks and moles?

U: Yes, birthmarks are of many colors and are formed because of many reasons. Moles on the other hand are caused by the clumping of pigment-producing cells.

J: Yes! And this is caused mainly due to mutations in DNA or other conditions that make cells clump and divide abnormally to receive birthmarks. And Dr. Bhatt spoke about what might trigger the cell to behave abnormally and turn into cancerous cells. What else did he say Utsuka?

U: He asked us to never stop talking with people about our questions. Just like the way Rythem talked to us about her questions.

J: But listeners, what we know about moles and birthmarks may change over time.

U: who knows one of our listeners might read about birthmarks and moles and find out something that we never knew before.

U: So that’s it for today.

J: If you want to know more about today’s scientist, we have linked his profile in the Show Notes!

U: If you have any questions that you want us to explore, shoot them away to Indiaakswhy@gmail.com

J: If you'd like to directly talk to us directly, then join the fun, join the fun on our Telegram Group. Link in the show notes.

U: For updates on IndiaAsksWhy, follow @IndiaAsksWhy on Twitter, and @India_AsksWhy on Instagram.

J: Shweata N. Hegde and Ruchi Manglunia are the hosts of the podcast.

U: Indulekha MS edited this episode.

J: and Khushi Goel transcribed it.

U: We are funded by IndiaBioscience’s second outreach grant.

J: Until next time. Till then, stay tuned and stay curious!