Entrevista al Dr. Jose Miguel Lizcano

“El laboratorio me atrapó: empiezas haciéndote una pregunta y luego te viene otra y ya no puedes parar”

El Dr. Jose Miguel Lizcano co-lidera el grupo de investigación Proteínas quinasas y transducción de señales. Según dice, va “donde estas proteínas le lleven: cáncer, Alzheimer, diabetes…”. Desde hace unos años, entre otros proyectos, está trabajando en colaboración con una empresa farmacéutica para desarrollar un fármaco anticancerígeno. Lo explicó en un seminario del Instituto hace unas semanas. La sala no podía estar más llena. Se me contagia su entusiasmo mientras le hago estas preguntas:

  1. Impartiste un seminario en el Instituto acerca de un fármaco antitumoral que estáis desarrollando. ¿Cómo empezó todo?

Un día de 2012, una empresa Biofarmacéutica, Ability Pharmaceuticals SL, llamó a nuestra puerta: tenían una molécula que, en estudios preliminares, parecía que podría funcionar como antitumoral. ¿Por qué funcionaba? Eso no lo sabían… Necesitaban inversores que les ayudaran a desarrollar el fármaco y los inversores no querían arriesgar si no tenían una idea de su mecanismo de acción. Por eso nos vinieron a buscar.

  1. ¿Y por qué a vosotros?

Porque los fármacos antitumorales normalmente actúan sobre las vías de señalización celular, que es lo que nosotros estudiamos. Somos expertos en unas proteínas que regulan estas vías: las proteínas quinasas, y vamos a donde ellas nos lleven: cáncer, Alzheimer, diabetes…

  1. ¿Qué son las vías de señalización?

Son circuitos de proteínas quinasas que se activan y se desactivan en cadena, las unas a las otras, para regular la vida de la célula. Cuando llega un impulso para que la célula se divida, por ejemplo, hay unas proteínas que se activan y hacen que se inicie el proceso. Cuando la división celular acaba, si todo funciona correctamente, estas proteínas se desactivarán. Sin embargo, puede suceder que haya una mutación y que una de estas proteínas reguladoras se quede siempre activada. Esto podría dar lugar a cáncer o a otras enfermedades: diabetes, enfermedades neurodegenerativas, etc.

  1. ¿Y qué descubristeis sobre el mecanismo de acción del fármaco?

Bien, la mayoría de los antitumorales que se utilizan hoy en día son fármacos quimioterápicos que provocan que las células tumorales mueran por apoptosis (un proceso que sucede constantemente en nuestro cuerpo por el que las células mueren de forma programada y ordenada). En cambio, comprobamos que el ABTL0812 utiliza otras vías para producir la muerte de estas células: provoca que el mecanismo de reciclaje celular, la autofagia, se acelere de forma masiva hasta que la célula no puede soportarlo y muere.

  1. Entonces, ¿sería una alternativa a la quimioterapia?

Más que una alternativa, creemos que puede funcionar muy bien en combinación con otros fármacos. Hemos visto que ABTL0812 potencia varias veces los efectos de la quimioterapia, de manera que si se administraran los dos fármacos simultáneamente, podría bajarse la dosis de quimioterapia y reducir sus efectos tóxicos.

  1. ¿Y este fármaco serviría para todos los tipos de cáncer?

Se ha demostrado in vitro y en modelos animales (ratones) que funciona en diversos tipos de tumores: páncreas, pulmón, endometrio, glioblastoma, neuroblastoma, etc. pero, por una decisión empresarial los estudios clínicos se dirigen a pacientes de cáncer de pulmón escamoso y cáncer de endometrio. Estos dos tipos de cáncer son muy agresivos y existen escasas opciones terapéuticas en el mercado, por lo que es más sencillo poder llevar a cabo los estudios clínicos.

Ahora el fármaco está en fase clínica 2, probando su eficacia en pacientes oncológicos. Para desarrollar esta fase del estudio, es necesario convencer al oncólogo de que lo pruebe en sus pacientes y esto es más fácil cuando hay pocas alternativas.

  1. Trabajáis con una farmacéutica bastante pequeña, ¿qué ventajas tiene trabajar con una compañía así respecto a con una gran industria?

Cuando estaba en Escocia trabajaba con farmacéuticas grandes y, aunque era muy interesante, me parecía que tenían mucha más información de la que me daban. La comunicación era muy diferente y la implicación también. Las compañías más pequeñas te permiten un trato personal y las complicidades que se establecen difícilmente las tendrás con las ‘big pharma’. Con esta empresa, que es un spin off del Parc de Recerca UAB, tenemos una relación muy estrecha.

Desde el principio hemos sido muy conscientes del poco dinero con el que contábamos, aunque la empresa ha hecho un muy buen trabajo para captar inversiones. Después conseguimos financiación pública: el MINECO nos concedió un proyecto INNPACTO, y se pudo contratar a la Dra. Tatiana Erazo, una investigadora muy competente que ha resultado clave en este estudio. Hemos tenido que procurar hacernos las preguntas adecuadas, para optimizar los recursos.

  1. El nombre del fármaco es un poco extraño… ¿De dónde viene?

No es un nombre comercial, todavía. De momento es solamente un código. Las letras vienen del nombre de la empresa: Ability Pharmaceuticals.

  1. Además de trabajar en “descifrar” exactamente el mecanismo de acción de este fármaco, ¿tenéis alguna otra línea de investigación activa en estos momentos?

Sí, también estamos buscando compuestos que inactiven o degraden la proteína ERK5, una quinasa que juega un papel primordial en cánceres de estirpe neuronal como el neuroblastoma y el glioblastoma.

Hacemos ciencia básica pero siempre buscando la traslacionalidad, que es algo que aprendí de la Dra. Mercedes Unzeta. Ella siempre decía: ‘estamos en la Facultad de Medicina, nuestra investigación tiene que poderse aplicar’.

Pienso que es muy importante hacer investigación básica, porque a veces nos centramos en las consecuencias de la enfermedad sin buscar las causas. Sin embargo, en los últimos años ha habido un gran recorte en las ayudas para la investigación en general, y en la investigación básica todavía más.

  1. De todos tus artículos, ¿cuál salvarías de un incendio?

El artículo central de mi tesis, porque eso es lo que me puso de alguna manera en el mapa. Era la primera vez que se purificaba la proteína con la que yo trabajaba. Lo publicamos en una buena revista.

  1. Cuándo estudiabas la carrera, ¿tenías claro que querías ser científico de laboratorio?

No. Empecé biología porque no sabía qué hacer. Después, cuando estuve en tercer curso, me decepcionó el hecho de tener que estudiar geología y otras materias que no me gustaban. Entonces, cambié de universidad y empecé bioquímica. En cuarto o quinto curso comencé a ir al laboratorio y me atrapó: empiezas haciéndote una pregunta y luego te viene otra y ya no puedes parar.

Pero bueno, realmente yo cuando tenía 18 años lo que quería ser músico. Guitarrista. En Escocia teníamos un grupo que se llamaba Sala4…

  1. ¿Cuándo fuiste a Escocia?

Fui ya mayor, con 34 años. Terminé la tesis y primero fui a hacer una estancia post-doctoral en el Trinity College de Dublín y luego, 6 años en Dundee, Escocia. Allí estuve en un centro top, el MRC Protein Phosphorylation Unit, que es un sitio muy competitivo donde había investigadores muy buenos de todo el mundo. Podía centrarme totalmente en el laboratorio sin tener que preocuparme por el dinero, porque teníamos muchos recursos. El límite lo ponía la capacidad de cada uno. Y descubrí que mi personalidad sirve para esto: soy perseverante, me gusta trabajar duro y tengo pasión por la ciencia.

Mi problema ahora  es que me gusta mucho el laboratorio pero entre el tiempo que dedico a buscar financiación y el que dedico a las clases, en el laboratorio puedo estar bien poco.

  1. ¿Volverías a irte al extranjero a hacer investigación?

Sí, pero es complicado. Somos profesores de universidad y no tenemos la capacidad de cambiar de institución. Antes había un programa de sabáticos pero ya hace años que se ha suspendido. Considero que esto no es bueno para un investigador: de la movilidad y del contacto con otros colegas te reciclas y sacas la motivación necesaria para seguir haciendo investigación competitiva.

A los que están empezando les diría que se vayan fuera y que exploren sus límites. Que viajen, que les dé el aire. Cambias de situación, de país, conoces a gente de todo el mundo que tiene tus mismos intereses… Vas ampliando el capital de tu cabeza, que es lo que importa. Las diferentes experiencias que vives son las que te van a dar un punto de vista único.

Roser Bastida Barau

Entrevista a la Dra. Roser Masgrau

“El calci és la base de tota la comunicació en els astròcits!”

Al sistema nerviós no només hi ha neurones. La Dra. Roser Masgrau, del grup de recerca Astrolab, va fer un seminari sobre els astròcits i com es comuniquen, i després vam poder fer-li aquesta entrevista:

  1. Què són els astròcits?

Els astròcits són un tipus de cèl·lules del sistema nerviós amb moltes funcions: aportar energia a les neurones, regular la comunicació sinàptica, participar en processos de reparació de dany neuronal, etc. Abans ens pensàvem que només servien per donar suport a les neurones, però ara s’està veient que tenen un paper molt més important que això. S’estan fent molts estudis per investigar, per exemple, la seva implicació en processos d’aprenentatge i memòria: sembla que podrien ser molt importants en l’emmagatzematge dels records mentre dormim…

  1. Quines diferències hi ha entre els astròcits i les neurones?

Morfològicament els astròcits són molt més ramificats. Constarien del soma i les múltiples ramificacions. Els astròcits també són territorials, tenen el seu territori i contacten i es comuniquen amb diferents tipus de cèl·lules.

I, és clar, les funcions entre neurones i astròcits són diferents.

  1. Sabem que les neurones entre elles es comuniquen a través de la sinapsi mitjançant els neurotransmissors. I els astròcits, poden comunicar-se entre ells o amb les neurones?

Sí! Els astròcits també s’envien missatges en forma de neurotransmissors (s’anomenen gliotransmissors si són alliberats pels astròcits), i també poden enviar i rebre transmissors cap a les neurones o de les neurones.

A més a més, els astròcits també es poden comunicar entre ells per contacte a través de GAP junxtions, per exemple.

  1. Quin paper hi juga el calci aquí?

El calci és la base de tota la comunicació en els astròcits! Quan arriba un missatge extracel·lular a l’astròcit, en forma de neurotransmissor per exemple, hi ha un canvi en la concentració d’ions calci a dins d’aquesta cèl·lula. Aquest canvi fa que l’astròcit elabori una resposta, com, per exemple, alliberar un gliotransmissor.

  1. D’on treu el calci, la cèl·lula, per excitar-se?

De l’espai extracel·lular o bé dels seus magatzems intracel·lulars. Una vegada originada la resposta,  el calci torna cap al magatzem o a l’espai extracel·lular.

  1. Fora del sistema nerviós, les altres cèl·lules, que no es comuniquen per sinapsi, també tenen aquests dipòsits de calci?

Sí, és una manera que tenen totes les cèl·lules de registrar estímuls extracel·lulars i/o elaborar respostes. Es fa servir en totes les cèl·lules: els miocits pel bateg del cor, o quaslevol cèl·lula muscular per contreure’s, per exemple.

  1. Aquest calci l’obtenim de la dieta?

Estem parlant d’una quantitat molt petita i que, a més, es va reciclant… Potser sí que indirectament alguna part es reposa de la dieta, però vaja, el calci que mengem, principalment va als ossos. Si bevem més llet no farem que les nostres cèl·lules es comuniquin millor, si és el que em preguntaves (riures)

  1. Hi ha alguna malaltia que estigui relacionada amb un mal funcionament del mecanisme del calci?

Sí, en algunes malalties neurodegeneratives, com en l’Alzheimer, s’ha vist que hi ha una alteració del funcionament del calci a les neurones i els astròcits. També pot estar implicat en la diabetis, en patologies cardíaques, etc.

  1. Quines línies de recerca teniu actualment?

D’una banda, estudiem com es regulen les senyals de calci en els astròcits, per tal de poder explicar la implicació d’aquestes cèl·lules en la memòria, i com aquest mecanisme està alterat en l’Alzheimer o en traumatismes cerebrals. I, per l’altra, estudiem un trastorn que es diu adrenoleucodistròfia, mirant la senyalització via calci entre d’altres processos bioquímics.

  1. De tots els articles que has publicat, quin creus que ha significat una aportació científica més gran?

Crec que en triaria un on demostràvem que hi havia, en concret, una via de senyalització del calci que estava implicada en la secreció d’insulina. Aquest article ha permès conèixer millor aquest procés i se n’han derivat molts estudis per trobar teràpies per la diabetis de tipus 2.

Roser Bastida Barau

 

Interview with Dr. James T Murray

“Autophagy is involved, in Type 2 diabetes, in neurodegenerative processes, in cancer… incidentally, many diseases that affect us as we age.”

Dr. James T Murray, from the School of Biochemistry and Immunology at the Trinity College in Dublin, gave a seminar at our Institute last month. It was a very interesting talk, mainly about how autophagy is involved in Parkinson’s disease. Just before the talk we had the chance to ask him a few questions…

  1. What is autophagy?

Cells get damaged. It is like a car: you have to service it; you have to put fuel into it, clean it, otherwise it doesn’t work as well. The autophagy pathway is a little bit like the servicing system for the cell. There are damaged materials, damaged organelles, misfolded proteins, and physiological stressors that cells must deal with. Autophagy is the mechanism by which the damage is removed before it becomes detrimental to cell viability. All eukaryotic cells have it so that they can be protected against environmental stress.

  1. How does it work?

It is similar to the endocytic pathway: a cellular structure is formed around the damaged material, to enclose it, that will eventually merge with a lysosome for the contents to be degraded. What is different, though, so the cell doesn’t get confused, is that in the autophagy pathway the vesicle has a double membrane, whereas in the endocytic pathway it is single. This double membrane vesicle that forms is called the autophagosome, and is usually spherical in shape. After the autophagosome finds and fuses with a lysosome, lysosomal enzymes begin to chop everything up, obtaining free fatty acids, amino acids, etc., and all the damaging materials are recycled.

  1. Why is it that we get old if our cells are recycling themselves to become new all the time?

My thinking is because the autophagy pathway becomes less profficient when we get older. This is because either the signals that control the autophagy pathway become less able to stimulate the response, the ability to package up damaged material is less efficient, or the amount of damage that needs clearing becomes too great for utophagy to cope with.

What I find fascinating is there is a little and very interesting organism, a salamander type creature that is called the olm, which lives in caves and can live for more than a hundred years. There is no natural light; there are no natural toxins, nor any predators in their environment. Once removed from normal physiological stresses they have adapted to a very long life span, for several reasons. I wonder whether there is anything special about their autophagy. If I had the opportunity, I would study the Olm.

  1. Aubrey de Grey is a British gerontologist who claims that, when we are able to fix the damage that we accumulate in our cells during our lives, humans will live for more than 1000 years…

No. I doubt we will ever live to 1000. We will get killed before that, we will probably be hit by a car! (Laughs) Theoretically I suppose yes, because if you can limit the amount of damage that occurs in tissues and organs, then there is no reason why cells, tissues and thus organisms can’t last for much longer periods of time, but to get to that point we would need a much greater understanding of ageing at a systemic level to be able to make the kinds of advances required to live so long.

  1. How can a cell know that it must recycle a specific organelle?

Well, I will use the example of the mitochondria. When this organelle works properly, a protein called PINK1 is constantly moved from the outside of the mitochondria, to the inside, where it is processed, then degraded. However, when mitochondrial function is compromised, PINK1 accumulates on the surface of the mitochondria, and this generates a signal that makes another protein, Parkin, functional. Parkin then activates other surface molecules, and these molecules act as signalling clues for destruction leading to selective autophagy of mitochondria, which is called mitophagy.

  1. What happens if the autophagy mechanism is not working properly?

Any fluctuations in normal autophagy have detrimental effects: both underactivity or the over-activity, and can lead to disease. Autophagy is involved, in Type 2 diabetes, in neurodegenerative processes, in cancer… incidentally, many diseases that affect us as we age.

  1. What happens in cancer?

It is complex: depending on the stage of the disease, autophagy is increased or decreased. In early stages of neoplastic diseases, autophagy is attenuated: there is an accumulation of damage that will produce the genetic lesions to activate oncogenes. This makes sense, because autophagy normally functions to eliminate damage, and so has what we consider tumour suppressor function. Then, when the primary tumour mass is forming, tumour cells and the surrounding normal tissue increase autophagy activity to provide nutrients for tumour cell growth and proliferation. Then, later, whenever tumours break away and tumour cells arrive at distant micrometastatic lesions through the circulation, autophagy comes into play again… It comes in waves that are complicit in cancer progression.

  1. And is any of the therapies used nowadays to treat cancer using the autophagy mechanism as their target?

One of the key responses to current chemotherapeutic drugs is chemotherapy resistance: patients become resistant to their first line treatment. In these chemoresistant tissues, the autophagy pathway frequently becomes activated, which is not surprising: you are insulting a tumour with a very large quantity of a toxic compound, so it will mobilize the autophagy pathway to try to limit damage. A new therapeutic strategy that is being explored is to deliver a combination treatment with standard chemotherapy agents and a drug that block the autophagy pathway, which currently are drugs that block lysosome activity. Drugs that are more selective for autophagy inhibition are still in the early stages of research development. We are also not certain of the long-term secondary effects of using specific autophagy inhibitors as drugs. So, yes: autophagy can be a very good druggable target, but it is unlikely that this strategy will work well enough on its own; modern oncology is tending towards multidrug cocktails.

  1. Today you are going to talk about autophagy in Parkinson’s disease. What is the relation between them?

Autophagy is essential for most aspects of the physiology of Parkinson’s disease. It is a multifactorial disease, which can be produced for many different kinds of protein mutations: in α–synuclein, in LRRK2, in PINK1, etc. These mutations can produce mitochondrial damage, which can eventually lead to an energy stress that can overwhelm and poison the autophagy pathway.

  1. What are you team currently working on?

Oh GOD, we work on a lot of different things!

Basically, we are interested in protein kinases and cell signalling processes that regulate autophagy. We study how these processes are involved in Parkinson’s disease, cancer, Alzheimer’s disease, type 2-diabetes, and also a rare disease called cystinosis. Well, and we also have a project on microglial function…the key point though is that much of the signals are common and so we can use our expertise to understand autophagy signaling in different contexts.

  1. If there was fire, and you could just safe one of your papers, which one would it be?

This is a hard one…! I think my first paper, as a PhD student. It was not a very spectacular publication, but it was my first. It was about kinases in macrophages, and I was very very proud of that work because I was able to mix enzymology, protein biochemistry and cell biology. That paper has really been the template approach I have tried to apply throughout my research career.

Roser Bastida Barau

Interview with Dr Joan Josep Guinovart

“We need to make people aware that they have to donate money for their universities, research centres, hospitals, etc.”

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Last Friday, October 14th, Dr Joan Josep Guinovart, Director of the Institut de Recerca Biomèdica de Barcelona (IRB), gave the Inaugural Lecture of the Official Master of Neuroscience at the Institute.

The Laia Acarin room was full of students and researchers of all ages listening to Dr Guinovart’s latest discoveries and research, which are focused on the negative consequences of the glycogen accumulation in neurons.

1- You are the director of the IRB and also the president of the International Union of Biochemistry and Molecular Biology. How can you reconcile the laboratory work with the management position?

This is the normal career for many people: first you are a student, then you are a post-doc researcher, after that you become a junior researcher of a leader, then if you are lucky they promote you, you get some leadership and management functions… and sometimes life make you assume big responsibilities.

I do go to the laboratory, but in the future I think I will like to be able to spend more time doing research. There is a moment in which you can leave responsibilities and come back to the start: it is like a cycle that it takes off and then suddenly descends.

2- Before you funded the IRB, an independent research centre, you were a researcher for a public university. Why did you decide not to do research from the university?

The decision was not made based on not doing research from the university, but rather the idea that I wanted to do research in a more interdisciplinary work environment. The university has the problem of being organized for teaching: colleges, departments, etc. Luckily nowadays this is in the process of being solved, because these separations in which researchers are working only with people of the same background are not good for research.

3- In what country would you like to do your research?

At my homeland, I’m completely ok about being here. I think that my whole life has been pulling and fighting for the research in Catalonia: to make it of international quality as it is nowadays.

4- Statistics shows that a few women have leadership positions in science. Do you think you would had more difficulties in your career if you had been a woman?

Sure! And I am so committed to change it. The problem is that it is not only depending of one thing, for which you can make a law or a general rule. The specific responsibility is not clear because it is something for the society at large. We have to change social attitudes, gender roles, men selfishness …

But I am so positive about it. It is changing so fast: around 100 years ago the society considered not appropriated for a woman to study medicine, and nowadays 70% of the medicine students are women. With management positions will be the same. Women are currently studying bachelor degrees, master degrees, PhD programs… the problem comes when they have to combine family and motherhood with science. We have to create the proper environments to make it possible. And I do not have any doubt that we will see it in just one generation. We have come a long way to reach to this point and we only need one step forward.

5- Two years ago IRB made a video in which scientists danced to raise funds. How is IRB funded?

The basic costs, such as turning on the lights or opening the doors, are supported by the Generalitat (The local Government of Catalonia), but research is funded by competitive Grant calls. We have quite a few European grants from the ERC and H2020 programs. However, what we need is more implication from philanthropy.

The big difference between our competitors, in the USA, and us is that, besides they receive more public funds, they also have a strong contribution from philanthropy and private funds. Here we need to make people aware that they have to donate money, not only for La Marató de TV3 (A very successful telethon organized for the local TV in Catalonia), but also for their universities, research centres, hospitals, etc.

The general complain is that the fiscal return is too little… But I don’t agree with that. You can donate up to 150 euros with a 75% fiscal return. And if everybody donated 150 euros it would be a lot!

6- So far the video has had more than one million visits…

Yes and apart for fundraising it has been very useful to make people know the IRB and to create a good attitude towards research, which benefits everybody.

7- Which of your qualities do you think that is the most important for being a good scientist?

The passion. You do research for two reasons: to escape from the distress of not knowing and for the pleasure of learning.

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8- Your research is focussed on the metabolism of glycogen. What is glycogen?

It is a glucose store to be used when we may need it.

9- And what does glycogen have to do with nervous system diseases?

It was thought that Glycogen did not have an important role in the nervous system but then it was discovered its presence in neurons and astrocytes. Neurons have an active metabolism of glycogen but they try not to accumulate it because it is harmful and may cause diseases.

10- In your opinion, what is the most promising therapeutic field?

It is the antibodies era. We are living the boom of therapeutic antibodies. Antibodies against molecules in the blood, against some specific receptors in specific cell types, etc. Antibodies bring the possibility of being very selective for a therapeutic target.

11- We read that your family had a cinema when you were a child and you spent many hours there. In that moment, what did you want to be when you grew up?

Well, look; one of my problems is that I do not know if I have reached my goals in life because I do not know what they were. I do not remember. And this makes me feel really frustrated… (Laughs)

Roser Bastida Barau

 

Interview with Dr Elisenda Sanz

“Neuroscience is one of the fields where one can expect the most significant advances to take place in the next few years”

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Dr Elisenda Sanz Iglesias, 37 years- Marie Sklodowska-Curie researcher Department of Cellular Biology, Physiology and Immunology Mitochondrial Neurohatology, Institut de Neurociències.

1.- How and why you ended up working as a neuroscientist?

After obtaining my Degree in Biology, it was clear to me that I wanted to pursue a career in Neuroscience. At that point, Dr. Mercè Unzeta from the Department of Biochemistry and Molecular Biology gave me the opportunity to join her group and obtain my PhD in the UAB’s Neuroscience program. This experience got me hooked on research and encouraged me to continue my training in this field (in which I already got the feeling that was going to be very stimulant)

2.-What research are you currently developing?

I’m currently developing novel tools for the cell type-specific isolation of mitochondria in complex tissues such as the brain. The brain contains multiple types and subtypes of cells, physically intermingled, which challenges the study of the cell-specific functions. In addition, mitochondria, which are known as the powerhouses of the cell, are cellular structures present in all cells. However, recent studies suggest that not all mitochondrial are equal, and that its composition and function is related to the cell type-specific environment. Our technology will provide the scientific community with a new tool that will allow the study of mitochondria at a level not currently attainable, and address the issue of cell type-specific mitochondrial heterogeneity.

3.-What are the major contributions in neuroscience in the past 20 years?

To me, one of the major contributions in Neuroscience in the last years has been the possibility to characterize and define, at an unprecedented level, all the different neuronal populations making up the brain. In the last years, a wide variety of tools
that allow for the dissection of neuronal complexity at all levels, from their transcriptional profile to its function and connectivity, have been developed. In my opinion, obtaining this level of resolution has been one of the major advances in Neuroscience in the last decade.

4.- Could you recommend us a research paper published during the last years?

I would suggest Ed Boyden and Karl Deisseroth’s paper where they describe for the first time the use of optogenetics to modulate neuronal activity (Boyden et al. (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci. 8(9):1263-8). Optogenetics have revolutionized the Neuroscience field. Therefore, this paper, along with the report describing the discovery process from the first author point of view (Boyden ES. A history of optogenetics: the development of tools for controlling brain circuits with light. F1000 Biol Rep. 2011; 3: 11), seem to me a quite stimulating read.

5.- How will you encourage future scientists to be part of Neuroscience research?

Neuroscience is one of the fields where one can expect the most significant advances to take place in the next few years due to the intense activity on the generation of novel tools and discovery technologies targeted to the nervous system that has taken and will take place during this decade. Neuroscience is a mystery in which there is still a lot to be discovered, and a significant part of this new knowledge, which has a direct impact on society, will be acquired in the next few years. It is not to be missed!

Interview with Dr Alfredo Miñano

“The more we know about our enigmatic brain, more new challenges appear in its complexity. More efforts are needed to find out why our central computer fails and to find a way to fix it.”

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Alfredo J. Miñano Molina, 36 years Postdoctoral Researcher Molecular and Cellular Basis of Neuronal Survival– Dr. José Rodríguez Álvarez.

1.- What research are you currently developing?

I am currently working in finding out which are the processes that are affected by the presence of beta-amyloid peptide at the synapses in the early stages of Alzheimer’s disease, resulting in their loss when neuronal death is still not occurring. The result of the progressive loss of synapses is the onset of cognitive deficits.

2.- How is the day-to-day inside your laboratory?

My day to day is pretty intense. The planning and organization of the group work in the laboratory is very important, so everyone who works in it can do it in the best conditions. One of my daily tasks is to ensure that the laboratory processes work perfectly. From there, you need to read to keep abreast of how science is going on in the world (as reading daily newspapers but at scientific level), consider this information and see how you can answer in the best way and with our resources issues that we are developing with our project. Here comes purely laboratory work: to plan experiments and carry them out. After that, analyzing the data and draw conclusions. Every week we have a day to share results with the rest of the group, to discuss the results and to see how we continue focusing our research. It is also very important to support students who are learning to move in a lab and those who are developing their thesis projects. It is key to having a reference nearby to help them learn to think and acquire their own criteria about the work they do every day and to be demanding with themselves. I try to help them with my experience to create solid foundations in their early formative stages as “scientifics.”

3.- What therapeutic applications do you think can your research have?

This is the fashionable research question, in this increasingly utilitarian world and how to respond it is what we are trying to learn in order to win points to get funds for our research. What we do should be useful to society (or any pharmaceutical company), and fast. Let’s see if you are convinced… We want to find out how are starting at synapses early symptoms of Alzheimer’s disease, because if we are able to do it we will know on what targets to act. We know that in these early processes there are altered molecules which are gaining importance in the recent years, that can give us clues about what is happening in the synapses long before the disease begins to manifest itself. These molecules can be analyzed using non-invasive methods for people. If we demonstrate the relationship between the alteration of one of these molecules and early-stages of the pathology, we will find a powerful therapeutic application with our work that could be useful to fight against the disease since the beginning.

4.- How you encourage future scientists to be part of neuroscience research?

The most important motivation is that biomedicine and neuroscience are the future. As time goes on, our life expectancy is higher. The more we know about our enigmatic brain, more new challenges appear in its complexity. More efforts are needed to find out why our central computer fails and to find a way to fix it. We can live a hundred years, but if you miss the computer that controls everything, what’s the use? I would encourage young people with talent, creativity and curiosity to know, to see in brain research the new challenges, and in neuroscience the way to develop their creativity to advance further in the knowledge of our brain. The question made by young people will be how to do it if this country is not committed to R & D? If there is enough motivation, dedication and desire we will succeed to convince people of this country about the importance of doing research. Doing outreach and education about what we do and why we do it, and if we get closer and people understand basic research as a leg of our society as they are health and education, then they will get pressured to change the research working in this country. If we think that many of these young people in ten or fifteen years will be leading research in the country, it is in their hands to fight for it.