Let’s introduce to our audience Dr. Sandra Acosta! Who are you? If you had to describe yourself in 1 sentence what would you say?

I am a neurobiologist working to understand how the human brain is built in health and disease.

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What are the most 

1- Fascinating research

2- Impactful research

3- Fun and whimsical research

You are leading these days?

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Understanding how the human brain acquires its very human traits, what makes our brain different to other species is a question that has been intriguing humanity since, at least, Ancient Greeks. It was Alcmaeon who brought up the role of the brain to control the body’s functions. Therefore, when our brain gets sick, it impacts the rest of the body. This is very obvious for instance when the patient suffers a stroke in the motor brain areas, the result is a body hemiplegia. And, the problem is that other brain disorders affect our most-human functions directly, our cognition, like Alzheimer’s Disease and other dementias, autism spectrum disorders or many psychiatric disorders. That is actually the frontline of research in my lab, trying to understand how the human brain is built and how it is affected at a molecular level when it is hit by a disorder. To reach those questions we are building little human brain models in a dish, a.k.a, organoids.. And, yes, that is fun. It’s like being a small kid playing lego. Developmental neurobiologists have studied how the animal neural tissue rises in the embryo (chick, frogs, salamanders, fishes, small mammals) for a century. And thanks to this knowledge we now know the biology and chemistry behind it. It is just a matter of adding the right proteins at the right time. Then, the cool thing is that once we instruct the cells properly with first signaling mechanisms, they grow into a brain by themselves.

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We hear a lot about Organoids…. What are they? What makes them so special? 

Organoids are organ models growing in a dish. We have lungs, kidneys, mammary glands, pancreas and of course, brains. The difference with traditional cell cultures is their ability to grow in volume, 3D, just like the organs, and therefore, they can integrate many other cell types and become really structurally complex. We make them out of pluripotent stem cells, from human cells or any other species. We call them induced pluripotent stem cells or iPSC. And we get them from any human individual donor. The combination of organoids and iPSC is really magical, we can study how each person’s genes condition the disease of a person in a human organ in a petri dish. This is really the personalized medicine future. For instance, in my lab, we are studying the potential risk of COVID-19 to generate dementia in the long-term, and to do that we use brain organoids as a shortcut, because in just a few months we can see if dementia cellular signs are showing up. But, also, we are centered in different disease strata. Is this neural damage occurring similarly and at the same pace, in a healthy person organoid than in an Alzheimer person? To do that we collaborate with the Barcelona Brain Research institute and Pasqual Maragall Foundation for Alzheimer’s, and virologists in Barcelona and all over Europe.

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Now let's talk about your work in gene therapy… are these permanent solutions? Are these genes passed to our kids? 

Gene therapy is really at the forefront of new therapeutical strategies and there is lots of power on it, because genes are controlling the response to damage. But, as a biologist I’m gonna give you some numbers that will solve the question. Only 1% of our genomes are genes and it is shared by all the cells in our body without exception. The other 99% are regulators that control when and in which organ the gene is expressed or not. So gene therapy could be delivered in specific tissues. There are only 2 cells in our bodies that can pass our genetic inheritance, the gametes (sperm and eggs), and they are genetically built very early in our in-utero development. So, if the gene therapy does not alter the gametes, no genetic information is going to pass to our offspring.Coming back to the first question, how permanent is the solution. That depends a lot on the kind of tool that it is used, and the cells that are targeted. Our body has a constant pool of stem cells replenishing tissues, specific in every organ. If you target those stem cells, with a tool that integrates in the genome, it can be permanent. But, it can also be an sporadic or chronic treatment.

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AI…AI…AI…is AI doing anything useful in your field as a neurobiologist?

Oh yes, for many years. Our experiments use an insane amount of data of different nature, microscopic images, genomic sequencing, etc. Without AI algorithms we literally won’t be able to analyze it. We are also contributing to the field generating new AI algorithms that can help automatizing and analyzing organoid datasets, reducing the researcher bias. That is particularly needed in our quest for providing  personalized medicine solutions to the disease that we are studying. 

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If you could design an experiment without any limitations of time or money…what would it be? 

Uf, can I choose many? I am very interested in trying to perturb gene expression in disease contexts, just modifying the regulatory networks in our genomes. Doing this in human brain organoids from several diseases to avoid the progression of the disease. At the end of the day, the brain is plastic, and if just a few neurons dye or “misbehave”, nothing will happen. But once a handful of neurons start misbehaving coordinately, they end up recruiting many others (disease progression). That is what I am tackling now. But are there common mechanisms, or different for every disease? Can we see real-time progression?

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If you could have a superhero power..What would it be?

Being at multiple places at the same time, for sure. 

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Mystery dinner party…Dead or Alive, who would be 3 guests you would invite to your dinner party?

Rita Levi Motalcini, Ernst Haeckel and Isabel Allende. The menu: caviar and my mum’s meatball soup.

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If you could leave a question for the next guest, what would that be? 

You’re an orchestra director, stranded in a remote place in the world (anywhere from the North Pole or the most remote part of Congo jungle). What would you play and what would you use as instruments?