IMAGES OF MEMORY:
A CONVERSATION WITH INES IBAÑEZ-TALLON

In this conversation, Dr. Ibañez-Tallon discusses why she became a neuroscientist, her current projects, the relationship between science and culture, as well as the preservation of cognitive function as one of the biggest frontiers in contemporary medical research.

Could you tell us about your background and how you decided to become a scientist?

I was born in Belgium and grew up in Barcelona—and my interest in science really took off shortly before I went to university there. I remember reading this article about how scientists started synthesizing insulin from plasmids, instead of extracting it from pigs. That was my first encounter with genetic engineering- what fascinated me was the idea that knowledge could be used to create new approaches to benefit people with a disease like diabetes.

I also like design, and my affinity for visual thinking was another factor that influenced my choice of science as a career. Scientists use images, schemes and graphs to explain complex concepts, like molecular cascades. Being able to visualize how molecules interact, how neurons connect in a circuit, sparks a whole new understanding of how we—human beings—work, and that has always been very appealing to me.

And how did you become interested in neuroscience specifically?

I chose to study biology rather than medicine because medicine requires a great deal of memorization and focuses less on understanding how things work, which has always been my passion.

After my degree in Biology I was awarded  a fellowship to pursue  a master’s degree in Belgium . Following that, I received another fellowship to complete my PhD in Italy, where I focused on transcriptional regulation in cancer cells.

I came to the US for a postdoc, and that’s when I began to shift toward neuroscience. My research until then had been very abstract – for example what happens to nucleosomes in gene promoters to regulate transcription.  When I started working with mice, studying neurons and how they connect to behavior, I realized that was what I wanted to do: understand how the brain functions.

What was so intriguing about the brain compared to your previous research?

I’m fascinated by neurons, the way they send messages to each other and somehow create a thought or an emotion that affects our behavior. To me, there’s something intrinsically beautiful.

I also think the brain is one of the last frontiers. Thanks to antibiotics and other advances, people now live into their 80s and 90s. We can renew the cells of our skin, hair follicles and muscle fibers, and we can get robotic replacements for so many parts of our bodies. Neurons, on the other hand, can’t be replaced and not even regenerated. We have the ones we were born with.

As people live longer than ever before, the experiences and wisdom we accumulate over a lifetime become increasingly valuable to share with younger generations. If we can live even a few years more, that would be significant. We’re all in the race to live longer, and the key is making these additional years worth living, instead of existing as a shadow of your former self.

Is that what led you to study Alzheimer’s disease?

My interest in Alzheimer’s is something that has evolved with the Fisher Center Lab. I know a lot of people come to this kind of research because of a personal story, after seeing their loved ones struggle with dementia.

For me it started with my work on addiction, studying nicotinic receptors in a particular brain area. That eventually led me to identify an orphan receptor important for addiction and neuropathic pain, and then Nat [Dr. Nathaniel Heintz, director of the Fisher Center Lab] suggested that I look at another orphan receptor, applying my knowledge to the study of memory and cognition.

And so far, that has been extremely interesting. Coming to a field after being trained in other areas allows you to bring a new perspective. I’m approaching Alzheimer’s looking at receptors no one has studied before and trying to understand the way in which exercise helps against the disease.

Right now, I’m working on three projects related to different aspects of Alzheimer’s disease.

The first one focuses on a receptor present in neurons that are important for memory, in a part of the brain called hippocampus. It’s an orphan receptor—meaning that we don’t know what molecules activate it. We found that it is expressed specifically in hippocampal neurons that degenerate very fast in the brains of Alzheimer’s patients.

We discovered that if we increase the expression of this receptor in mice, the neurons with more receptors become more active and preserve much better cognitive function. The mice have much better associative memory, and they also find it easier to remember places they’ve been before.

Neurons can’t be replaced, as I said—once they’re gone, they’re gone. So the idea is that if we can keep the hippocampal neurons active by increasing the activity or the amount of receptor they express, then we might be able to preserve them from the disease, before degeneration occurs.

What is your second project about?

In our second project we are working to understand why exercise is good for the brain. Exercise can reduce Alzheimer’s risk, so it has an impact on the prevention of the disease.

Mice love to run, like hamsters—females can run up to ten kilometers in a single night. For this study we are comparing the neurons of mice that run to those of mice that don’t, to see if there are any differences.

We have identified specific neurons that are important for running—we noticed that if they are damaged, the mice don’t want to run anymore. We are looking at these neurons in runners and non-runners to figure out which genes differ between the two groups.

The goal is to translate something that we know to be good for the brain—exercise—into a precise molecular understanding of what makes it beneficial. I find this fascinating—human beings evolved running in fields, after all, not sitting at desks. I want to study the brain not as a static thing, but as an organ that is both plastic and adaptable—much more than we often assume it to be.

What is the third project you are working on?

The last project is a collaboration with teams in the lab using human brain samples to piece together a particular molecular cascade that occurs in Alzheimer’s disease. Alzheimer’s starts in the hippocampus and from there it spreads to the cortex. We’re trying to understand this molecular process as it affects both parts of the brain.

This project is more about data analysis and integration than hands-on experiments. My colleagues have collected extensive data from the hippocampus and the cortex of post-mortem brain samples, and we are now combining these data to understand how it all fits together.

Our aim is to delineate the molecular cascade that takes place in human brains at different stages of AD. Unfortunately, that is also why this project highlights a key limitation—because we can collect information from post-mortem brain samples, but obviously we cannot use them to observe how molecules behave in a living brain.

To get around this problem, we are using mouse models where we can manipulate specific elements based on our observations. That will help us gain better insight into the progression of the disease and also identify points of therapeutic intervention at a molecular level.

I enjoy abstract painting, being in nature and traveling to different countries. That’s another reason I like being a scientist. I have lived in five countries and worked with people from different backgrounds. This has allowed me to understand how differently research is done in different places, and why what is done in one country may not be possible in another.

People don’t often associate cultural variability with science, but in my experience, it has a very significant impact. People who study from the same textbooks will naturally think along relatively similar lines. People from different places, by contrast, often bring to the table approaches that can be very surprising—and extremely useful, as well.