Dr. Ilary Allodi
Principal Investigator and Assistant Professor at University of Copenhagen, Denmark
Lecturer University of St. Andrews
Postdoctoral Fellow Karolinska Institute (Stockholm, Sweden) and University of Copenhagen
PhD in Neuroscience Universitat Autonoma de Barcelona, Spain
It is fitting that Dr. Ilary Allodi, who enjoys writing short stories in her free time, began her foray into neuroscience with a book. As a teenager, Ilary read Searching for Memory by Daniel Schacter, which details the psychological mechanisms of memory, drawing substantially from the lessons of unique clinical cases. This book piqued her curiosity about the brain and in particular, the changes that occur during disease. Ilary continues to be motivated and inspired by the clinical cases and human experiences that underlie many of the research questions in neuroscience. Now, as a principal investigator at the University of Copenhagen and a lecturer at the University of St. Andrews in Scotland, Ilary studies motor neuron degeneration in the context of amyotrophic lateral sclerosis (ALS).
Given her early interest in psychology in a clinical setting, Ilary decided to pursue a degree in neuropsychology when she began as an undergraduate at the University of Turin. Her coursework perfectly melded with her interests, and as she wrapped up her undergraduate studies, she was excited to begin applying her newfound knowledge to the clinical realm working with patients. She was accepted for an internship at a hospital in Turin. Patients at the hospital often had progressive and untreatable neurological disorders. Ilary remembers a patient with frontotemporal dementia and ALS who was the same age as her father and had a son born on the same exact day as Ilary. ALS is a disease that causes degeneration of the neurons that control one’s muscles (called motor neurons), causing a progressive loss of muscle functioning. It is generally fatal within three to five years of diagnosis (source). This case was heartbreaking to Ilary, given that there are no cures or effective treatments for dementia and ALS. The similarities between her family and the patient’s put in sharp relief that this family’s experience could have been her own.
Facing this feeling of powerlessness within a clinical setting, Ilary decided to turn to basic research, where she hoped to contribute to the effort to find treatments for these diseases. However, all her training thus far had been in clinical psychology, and she had no wet lab experience. Prof. Ferdinando Rossi, a professor from her undergraduate training, gave Ilary the chance to explore working in a research setting, accepting her as a master’s student in his lab. Ilary took baby steps, learning immunohistochemistry, in vitro culture methods, and soon, with some apprehension, rodent handling. Ilary enjoyed lab work immensely and hoped to pursue a PhD. Ferdinando, impressed by her capabilities, encouraged her to apply for the Marie Curie Initial Training Network, a prestigious PhD fellowship. Ilary was worried that her training as a psychologist made her unqualified. However, Prof. Rossi was quick to assuage this fear, telling Ilary that there was nothing about being a psychologist by training that would prevent her from being a good neuroscientist. With the encouragement of her PI, Ilary applied to an open PhD position funded by the fellowship at the Universitat Autònoma de Barcelona.
When Ilary found out she was accepted for the fellowship, she was overjoyed. She moved to Spain to pursue her PhD with Profs. Xavier Navarro and Esther Udina. Deeply impacted by her previous work with ALS patients, Ilary took on a project studying motor neuron regeneration with the hopes that understanding how this regeneration works could help scientists find a way to prevent or reduce the impact of motor neuron degeneration in conditions like ALS.
Ilary’s model system was a 3D culture model of motor neurons, into which she added several different types of molecular cues to evaluate their impact on the capacity of the motor neurons to regenerate. She found that a subset of these cues, a combination of trophic factors and integrins, were able to induce regeneration. However, even within the 3D culture, which is highly controlled, there was still heterogeneity in how the motor neurons regenerated. Some developed beautiful processes, and others seemed to remain quiescent, or died. Given that the cells were all in the same environment, Ilary hypothesized that something intrinsic to the cell was driving this heterogeneity and hoped to deduce what it was.
With this hypothesis in mind, Ilary interviewed for her first postdoc position with Dr. Eva Hedlund at the Karolinska Institutet. Eva had just published a large transcriptomics study comparing motor neurons that are resistant to ALS (oculomotor neurons) with other motor neurons in the brain and spinal cord that are more vulnerable. This project meshed well with Ilary’s question about the heterogeneity in regenerative properties across motor neurons. During her postdoc, Ilary helped develop a stem cell-derived model of oculomotor neurons. She then demonstrated that these ALS-resistant motor neurons express pro-survival signaling molecules and are more resilient to excitotoxicity, or the death of a neuron due to high levels of neurotransmitter stimulation.
At Karolinska, Ilary found herself surrounded by people researching motor control, focusing on the circuit level questions about motor neurons as opposed to the more cellular-level questions she typically focused on. Ilary was fascinated by the topic and was particularly inspired by a department seminar on motor circuitries given by Prof. Ole Kiehn. This was Ilary’s eureka moment; she had previously focused on which intrinsic properties of individual motor neurons made them more likely to regenerate or degenerate. What if, instead of a single cell being more vulnerable to these processes, it was the circuits that contained them? Perhaps, she thought, the inhibitory cells (termed interneurons) that connected to the motor neurons were also malfunctioning, driving maladaptive changes in motor neurons. Ilary hoped to study this question in the context of ALS.
Ilary applied for funding for this project but was unsuccessful. The prevailing dogma was that interneurons weren’t that important to the disease, and research should instead focus on motor neurons. However, unwilling to give up on the idea, she took it to Ole. He thought it was marvelous, and suggested they apply for funding together. She then joined his lab at the University of Copenhagen for her second postdoc. She found that, in an ALS mouse model, there was a progressive loss of inhibitory synapses onto the motor neurons which innervate fast twitch muscle fibers and are more vulnerable to ALS. She found that the degeneration of the interneurons preceded the degeneration of motor neurons, and that this degeneration of interneurons correlates with behavioral changes.
Three years into her second postdoc, Ilary applied for and was accepted to an Assistant Professor position at the University of Copenhagen. Ilary’s lab’s research is, in many ways, a continuation of the idea she posited to Ole at the start of her second postdoc; she continues to study the circuit level progression of ALS and now has extended her research to frontotemporal dementia. Her science is also still deeply affected by her past experiences with patients; she focuses on projects that are translational, and that could one day enter a clinical trial and provide treatment for the patients she once cared for. Ilary’s early years working with patients also made clear the importance of studying subtle changes in behavior to delve into the progression of a pathology. Her lab uses machine learning tools to determine the first, most subtle changes and symptoms of a disease, and correlates the onset of these different behaviors with changes in the circuits.
When Ilary started her lab, she found that the day-to-day life of her job radically changed. Ilary is delighted by these newfound responsibilities and enjoys grant writing, supervising, and even reviewing papers. As Ilary reflects on how she mentors her own students now, she notes that women in science are not often encouraged or supported in the pursuit of high-risk projects. She professes gratitude for her own mentors, who trusted her and gave her the space to take risks. She hopes to encourage the same high-risk projects in her own students’ careers and provide the support required for this type of science. Given Ilary’s infectious enthusiasm, bold ideas, and profound care for the human lives that depend on science, her lab’s research will certainly continue to significantly advance our understanding of ALS and other degenerative conditions.
Find out more about Ilary and her lab’s research here.
Listen to Margarida’s full interview with Ilary on November 24, 2022 below!
