Science Space
Sérgio de Almeida and his new weapon in the fight against breast cancer
<img class="aligncenter wp-image-26953" src="http://news.medicina.ulisboa.pt/wp-content/uploads/2018/10/Sergio-de-Almeida-Perfil.png" alt="" width="640" height="448" />
Sérgio de Almeida is 39 years old and is one of the main researchers of the iMM and a teacher at FMUL. He was born in Castro Daire, but he went to study in Viseu at an early age, as he realised that he needed to broaden his horizons to gain experience and knowledge. He graduated in Biochemistry in Coimbra and completed his PhD in Biomedical Sciences in Porto. Because he wanted to be a scientist, he knew he had to do his post-doctoral studies and that's why he moved to Lisbon. He chose Carmo Fonseca's Laboratory at the iMM. After that, he grew up on his own, raised doubts, asked questions, and sought answers. He asked basic research questions, a name he's not very fond of because he firmly believes that "research is either good or bad, the rest stems from that". Some of the questions he asked came to have an impact on cancer, but when he brings ideas to the table and asks new questions, he's not focusing specifically on cancer, because his field of work is DNA.
Currently a team leader at iMM, Sérgio de Almeida has recently been awarded an iMM-Laço Fund grant, fully financed by Pioneer, for a research on breast cancer, coincidences of studies that intersect in common ideas. "It all started with a very fundamental research project, with a paper we published early in 2017 and that touches very lightly on the issue of cancer. A process that describes fundamental issues and which, in the meantime, we realised had a lot of potential to become something very relevant, specifically regarding breast cancer, but going beyond that."
With 25 thousand euros from the iMM-Laço Fund to increase his focus on breast cancer, Sérgio is able to rely on other funding resources, the last one granted by the FCT (Foundation for Science and Technology), which allows him to continuously develop his research and work with an 8-member team. He doesn't spend as much time at the bench as he used to in the beginning, but he still does it when he needs to teach some method to new arrivals; there are people in his team who can teach for him, but he goes back to basics when there is a need to clear doubts or help the newest team members. What he misses most about working at the bench is the moment when he said "eureka, I discovered this and I was the first one to see it under the microscope"; now he's coordinating those who work at the bench to allow them to makes discoveries as he did. Teaching is a task he loves and does not push into the background.
This passion for explaining why things happen makes sense to someone who is also a teacher of 1st-year Molecular Biology of the Cell and 3rd-year Oncobiology at the Faculty of Medicine of the University of Lisbon.
Working on the 3rd floor of the iMM he welcomes me to talk about the research he's developing for the iMM-Laço Fund, but I quickly realize that he has a passion not just for Science, but also for the challenge of the daily contact between students and Teacher, and one can feel this because he explains Science in a way that makes us think it's actually simple.
You told me that you're always looking for questions. What was the question you were trying to answer for this research that touched on the topic of breast cancer?
Sérgio de Almeida: I use the metaphor of a ship to explain the purpose of the research because it's easier to understand. We are going to study a very specific breast cancer, which is the hormone-dependent cancer, the most common one, usually the one that most women heard about and which has a good prognosis. The treatment is hormone-based, and not as aggressive as chemo- and radiotherapy-based treatments. The question we asked, and comparing these cancers to a ship, was: a ship that is sailing at a very high speed in a very rough sea will most likely let water in. Now imagine that this water are lesions that cancer cells accumulate in your DNA. Because the cells proliferate very quickly, they will accumulate many lesions. And what happens? Just as a ship has a crew responsible for pumping the water out of the ship so it doesn't sink, we also found out that, in cells that are proliferating very fast, there are molecules that prevent the effect of DNA lesions, allowing those cells to be able to continue to proliferate, and allowing the tumour to grow.
So, when we were faced with this scenario, the question we asked was: How can we sink this ship that is sailing at a high speed? We get rid of the crew that is pumping out the water and with that we cause only a minor impact on the little ships that are sailing at a much lower speed around it, as little water gets into them. If our strategy were to pour even more water into the ship so it would sink, we would damage the little ships around it. That would be the effect of a treatment like chemotherapy, it would create even more lesions with many side effects. That's what we discovered. If we eliminate this crew in a normal cell, it carries on with its normal life because it's not proliferating at such a great speed. If the hormone-dependent breast tumour cells are deprived of this crew, i.e., of this molecule, they will die..
But that would be an exceptional breakthrough.
Sérgio de Almeida: And we think it is. In fact, we are currently discussing a transfer of technology and intellectual property so it can be materialised. But that goes beyond what we do here in the Lab and involves other partners and other financial resources. But in the lab, in vitro and in cell cultures, we see that if we have a cell culture that is not a hormone-dependent breast cancer, and a cell culture that is hormone-dependent, when we eliminate this molecule in the hormone-dependent culture, the cells die; in the others, the cells carry on with their perfect lives. So what we think we have here is a highly-specific therapy that we believe will have very few side effects.
And do you know how you will eliminate those molecules?
Sérgio de Almeida: In the lab, in cell cultures, we are able to pursue different experimental approaches to eliminate the molecules. We are able to interfere with the expression of the gene that gives rise to this molecule; this is possible in the lab, but doing this on a person is a lot more complicated. But, of course, there is always the possibility of developing a drug, a chemical agent, that will selectively inhibit the molecule. Our intervention ends when we identify a druggable target, i.e., a target that is rendered inactive by a chemical. Our proof of concept, which is the validation of the original hypothesis, has been established, i.e., we have achieved what we wanted to in our in vitro experimentation. And that happened this past year with the funds of this grant (iMM-Laço).
But after this question there is always another question, right?
Sérgio de Almeida: There is no shortage of questions...
Does a Group Leader take the bench??
Sérgio de Almeida: Sometimes; I do, when there is the need to teach someone, and some things I like to teach myself, because I like things to be done exactly as I do them. But I'm taking the bench less and less, because I'm lucky enough to have people to teach new arrivals. I don't take the bench to make experiments as much as I used to, but I sit with other people at the bench to analyse results, that I do quite often.
You were just telling me that you teach 1st-year students and then 3rd-year students at the Faculty. Do you see any evolution from one year to the other and any difference in their engagement as students?
Sérgio de Almeida: The difference is quite clear. I teach the 1st year, in the 1st semester. I find them very frightened, very overwhelmed with Anatomy, which is very exhausting for them, because it's a very demanding subject. In the 3rd year, I teach many of my former 1st-year students and it's very interesting, mainly in terms of self-confidence and attitude in class, it's amazing. They really do grow up! They are much more confident and believe a lot more in what they know, they present and discuss issues in a more authoritative way, and they don't take everything for granted anymore; they also ask "why" a lot.
And is it challenging for you, as a Professor, to have someone who tries to argue and even contradict you?
Sérgio de Almeida: But that's exactly how it is! And if it's not, then classes aren't even interesting. If I go there and simply pass on information, then I don't even need to be specially trained as a University Professor; anyone can show a series of slides and tell them what they need to study. If there is no interaction between the Professor and the students, if the Professor doesn't satisfy the students' curiosity, meaning that he needs to be prepared and have a much more extensive knowledge, then he's not very useful.
So, the challenge for you is in the debate?
Sérgio de Almeida: Yes, that's exactly why I like to teach. I like teaching more and more each day. At first, because my career was a lot more related to research, I was afraid that teaching would take time away from research. But I realised it didn't. I enjoy giving classes more and more each day. Because, sometimes, students ask questions that put certain things in a totally different perspective. I always remember Sydney, he is a very respected man in the scientific community who wrote a letter in which he began by saying: "I'm a firm believer in the power of "ignorance". I think we may always know too much". This phrase perfectly reflects the opportunities we have to learn with students, even with 1st-year students, because this "ignorance" is synonymous with naivety, not with illiteracy. But he keeps going in his letter and says that these students who arrive at the campus when they're very young are those who often make great discoveries. Those who have been working on the same topic for a long time know too many reasons why a certain experiment will not work, and their reasoning is very much biased. When a kid who has just arrived asks a question, he will try to answer it. Sometimes the answer is surprising and it's something that no one was expecting. That is why in my Lab, and this is very visible in our publications, we don't publish the same topic over and over; we obviously have a common denominator, but we vary the sub-topic. I try not to work for too long on the same subject, because we limit ourselves to incremental research and that just makes us walk around in circles. If we choose new topics, we have to study a lot, but that allows us to ask new questions, which may seem basic for those who have been working in the field for too long, but that may be more challenging for us.
It's thanks to this desire to step into unknown territory that many scientists, researchers, professors, and physicians try to find explanations for things that no one has yet been able to understand. Bypassing the limits imposed by nature and pursuing the challenges imposed by the human body is what moves us.
That person who was once a young student, who decided that his town was not enough for him to grow, is now educating students and his own children based on the belief that confidences allows us to reach the highest quality levels. Sérgio de Almeida seeks excellence and believes the future generations will continue to do more and better.
The 25 thousand euros of the iMM-Laço Fund allowed to him to carry out tests in vitro cultures and to validate the proof of concept.
To the sum of the wills of all these Laboratories it is imperative to add funds and government aids, and only then, even if not in our generation, will we be able to defeat breast cancer and other cancers, as well as many other diseases. That's the only way to keep the circle of discovery alive.
Find out more about the research work developed by the iMM-Laço Fund:
https://youtu.be/AxxzKCMsWpI
Joana Sousa
Equipa Editorial
Sérgio de Almeida is 39 years old and is one of the main researchers of the iMM and a teacher at FMUL. He was born in Castro Daire, but he went to study in Viseu at an early age, as he realised that he needed to broaden his horizons to gain experience and knowledge. He graduated in Biochemistry in Coimbra and completed his PhD in Biomedical Sciences in Porto. Because he wanted to be a scientist, he knew he had to do his post-doctoral studies and that's why he moved to Lisbon. He chose Carmo Fonseca's Laboratory at the iMM. After that, he grew up on his own, raised doubts, asked questions, and sought answers. He asked basic research questions, a name he's not very fond of because he firmly believes that "research is either good or bad, the rest stems from that". Some of the questions he asked came to have an impact on cancer, but when he brings ideas to the table and asks new questions, he's not focusing specifically on cancer, because his field of work is DNA.
Currently a team leader at iMM, Sérgio de Almeida has recently been awarded an iMM-Laço Fund grant, fully financed by Pioneer, for a research on breast cancer, coincidences of studies that intersect in common ideas. "It all started with a very fundamental research project, with a paper we published early in 2017 and that touches very lightly on the issue of cancer. A process that describes fundamental issues and which, in the meantime, we realised had a lot of potential to become something very relevant, specifically regarding breast cancer, but going beyond that."
With 25 thousand euros from the iMM-Laço Fund to increase his focus on breast cancer, Sérgio is able to rely on other funding resources, the last one granted by the FCT (Foundation for Science and Technology), which allows him to continuously develop his research and work with an 8-member team. He doesn't spend as much time at the bench as he used to in the beginning, but he still does it when he needs to teach some method to new arrivals; there are people in his team who can teach for him, but he goes back to basics when there is a need to clear doubts or help the newest team members. What he misses most about working at the bench is the moment when he said "eureka, I discovered this and I was the first one to see it under the microscope"; now he's coordinating those who work at the bench to allow them to makes discoveries as he did. Teaching is a task he loves and does not push into the background.
This passion for explaining why things happen makes sense to someone who is also a teacher of 1st-year Molecular Biology of the Cell and 3rd-year Oncobiology at the Faculty of Medicine of the University of Lisbon.
Working on the 3rd floor of the iMM he welcomes me to talk about the research he's developing for the iMM-Laço Fund, but I quickly realize that he has a passion not just for Science, but also for the challenge of the daily contact between students and Teacher, and one can feel this because he explains Science in a way that makes us think it's actually simple.
You told me that you're always looking for questions. What was the question you were trying to answer for this research that touched on the topic of breast cancer?
Sérgio de Almeida: I use the metaphor of a ship to explain the purpose of the research because it's easier to understand. We are going to study a very specific breast cancer, which is the hormone-dependent cancer, the most common one, usually the one that most women heard about and which has a good prognosis. The treatment is hormone-based, and not as aggressive as chemo- and radiotherapy-based treatments. The question we asked, and comparing these cancers to a ship, was: a ship that is sailing at a very high speed in a very rough sea will most likely let water in. Now imagine that this water are lesions that cancer cells accumulate in your DNA. Because the cells proliferate very quickly, they will accumulate many lesions. And what happens? Just as a ship has a crew responsible for pumping the water out of the ship so it doesn't sink, we also found out that, in cells that are proliferating very fast, there are molecules that prevent the effect of DNA lesions, allowing those cells to be able to continue to proliferate, and allowing the tumour to grow.
So, when we were faced with this scenario, the question we asked was: How can we sink this ship that is sailing at a high speed? We get rid of the crew that is pumping out the water and with that we cause only a minor impact on the little ships that are sailing at a much lower speed around it, as little water gets into them. If our strategy were to pour even more water into the ship so it would sink, we would damage the little ships around it. That would be the effect of a treatment like chemotherapy, it would create even more lesions with many side effects. That's what we discovered. If we eliminate this crew in a normal cell, it carries on with its normal life because it's not proliferating at such a great speed. If the hormone-dependent breast tumour cells are deprived of this crew, i.e., of this molecule, they will die..
But that would be an exceptional breakthrough.
Sérgio de Almeida: And we think it is. In fact, we are currently discussing a transfer of technology and intellectual property so it can be materialised. But that goes beyond what we do here in the Lab and involves other partners and other financial resources. But in the lab, in vitro and in cell cultures, we see that if we have a cell culture that is not a hormone-dependent breast cancer, and a cell culture that is hormone-dependent, when we eliminate this molecule in the hormone-dependent culture, the cells die; in the others, the cells carry on with their perfect lives. So what we think we have here is a highly-specific therapy that we believe will have very few side effects.
And do you know how you will eliminate those molecules?
Sérgio de Almeida: In the lab, in cell cultures, we are able to pursue different experimental approaches to eliminate the molecules. We are able to interfere with the expression of the gene that gives rise to this molecule; this is possible in the lab, but doing this on a person is a lot more complicated. But, of course, there is always the possibility of developing a drug, a chemical agent, that will selectively inhibit the molecule. Our intervention ends when we identify a druggable target, i.e., a target that is rendered inactive by a chemical. Our proof of concept, which is the validation of the original hypothesis, has been established, i.e., we have achieved what we wanted to in our in vitro experimentation. And that happened this past year with the funds of this grant (iMM-Laço).
But after this question there is always another question, right?
Sérgio de Almeida: There is no shortage of questions...
Does a Group Leader take the bench??
Sérgio de Almeida: Sometimes; I do, when there is the need to teach someone, and some things I like to teach myself, because I like things to be done exactly as I do them. But I'm taking the bench less and less, because I'm lucky enough to have people to teach new arrivals. I don't take the bench to make experiments as much as I used to, but I sit with other people at the bench to analyse results, that I do quite often.
You were just telling me that you teach 1st-year students and then 3rd-year students at the Faculty. Do you see any evolution from one year to the other and any difference in their engagement as students?
Sérgio de Almeida: The difference is quite clear. I teach the 1st year, in the 1st semester. I find them very frightened, very overwhelmed with Anatomy, which is very exhausting for them, because it's a very demanding subject. In the 3rd year, I teach many of my former 1st-year students and it's very interesting, mainly in terms of self-confidence and attitude in class, it's amazing. They really do grow up! They are much more confident and believe a lot more in what they know, they present and discuss issues in a more authoritative way, and they don't take everything for granted anymore; they also ask "why" a lot.
And is it challenging for you, as a Professor, to have someone who tries to argue and even contradict you?
Sérgio de Almeida: But that's exactly how it is! And if it's not, then classes aren't even interesting. If I go there and simply pass on information, then I don't even need to be specially trained as a University Professor; anyone can show a series of slides and tell them what they need to study. If there is no interaction between the Professor and the students, if the Professor doesn't satisfy the students' curiosity, meaning that he needs to be prepared and have a much more extensive knowledge, then he's not very useful.
So, the challenge for you is in the debate?
Sérgio de Almeida: Yes, that's exactly why I like to teach. I like teaching more and more each day. At first, because my career was a lot more related to research, I was afraid that teaching would take time away from research. But I realised it didn't. I enjoy giving classes more and more each day. Because, sometimes, students ask questions that put certain things in a totally different perspective. I always remember Sydney, he is a very respected man in the scientific community who wrote a letter in which he began by saying: "I'm a firm believer in the power of "ignorance". I think we may always know too much". This phrase perfectly reflects the opportunities we have to learn with students, even with 1st-year students, because this "ignorance" is synonymous with naivety, not with illiteracy. But he keeps going in his letter and says that these students who arrive at the campus when they're very young are those who often make great discoveries. Those who have been working on the same topic for a long time know too many reasons why a certain experiment will not work, and their reasoning is very much biased. When a kid who has just arrived asks a question, he will try to answer it. Sometimes the answer is surprising and it's something that no one was expecting. That is why in my Lab, and this is very visible in our publications, we don't publish the same topic over and over; we obviously have a common denominator, but we vary the sub-topic. I try not to work for too long on the same subject, because we limit ourselves to incremental research and that just makes us walk around in circles. If we choose new topics, we have to study a lot, but that allows us to ask new questions, which may seem basic for those who have been working in the field for too long, but that may be more challenging for us.
It's thanks to this desire to step into unknown territory that many scientists, researchers, professors, and physicians try to find explanations for things that no one has yet been able to understand. Bypassing the limits imposed by nature and pursuing the challenges imposed by the human body is what moves us.
That person who was once a young student, who decided that his town was not enough for him to grow, is now educating students and his own children based on the belief that confidences allows us to reach the highest quality levels. Sérgio de Almeida seeks excellence and believes the future generations will continue to do more and better.
The 25 thousand euros of the iMM-Laço Fund allowed to him to carry out tests in vitro cultures and to validate the proof of concept.
To the sum of the wills of all these Laboratories it is imperative to add funds and government aids, and only then, even if not in our generation, will we be able to defeat breast cancer and other cancers, as well as many other diseases. That's the only way to keep the circle of discovery alive.
Find out more about the research work developed by the iMM-Laço Fund:
https://youtu.be/AxxzKCMsWpI
Joana Sousa
Equipa Editorial
