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September 18, 2023

Sandra Siegert Promoted to Professor

Her research on microglia has new vigor as her start-up launches

A scientific journey that began in Bad Camberg, a small town in Germany, has reached a major milestone at the Institute of Science and Technology Austria with the Professorship of Sandra Siegert coming into effect this month.

Professor Sandra Siegert investigates the role of microglia in the healthy and diseased brain. © Peter Rigaud/ISTA

After working at MIT, Siegert joined the Institute of Science and Technology Austria (ISTA) in 2015 as an Assistant Professor. Since the time she set up her lab here, she has heightened the scientific know-how on microglia – the important immune cells of the nervous system. Her research has been awarded several prizes and received international funding, most recently from the ERC and a stand-alone grant from FWF.

“It is with great pleasure that I am announcing the promotion of Sandra Siegert to Professor for her notable contributions on the role of microglia in the nervous system. Please join me in congratulating her,” said Martin Hetzer, President of ISTA in an email to the campus community announcing her professorship.

Courageous decisions

Siegert has proudly journeyed in research with a passion and creativity for science. She says this has been possible with the support of mentors encouraging and guiding her to transcend barriers she has and is still facing. Coming from a working-class background, Siegert says she has always been the “first in every career step” in her family. Already in primary school, she was driven to go forward. “I knew that my job perspectives would be better with a higher education. But considering to study at university felt somehow off and required courage,” she shares.

A science summer camp held at the TU Darmstadt prodded a young Siegert to think about science as a career choice. “In those two weeks performing experiments and working with chemicals drove my interests in natural sciences,” she laughs. “I loved mathematics, especially calculus, but algebra and stochastic killed me. In biology class, we had just started with neuroscience and genetics.” She remembers that she gave a short presentation about the function of the cerebellum. “After the presentation, I was hooked to understand how our brain works”.

The path to her own research group

Siegert studied biology at the Johann Wolfgang Goethe University in Frankfurt/Main. During the semester breaks, she volunteered for internships in different labs amongst them one at the Max Plank Institute of Brain Research. “This was the first time I got in touch with the visual system while we analyzed the distribution of cone and rod photoreceptors in retinas of different species.” This was just only the beginning of her pursuit to resolve the morphological complexity of the retina. After an excursion for her diplomathesis in virology to verify gene therapy approaches against HIV-1, she settled on developing her own research project.

Her scientific journey covered many miles. She moved to Switzerland for her PhD, where she resolved the gene transcriptional diversity of retinal cell types allowing cell type-specific therapeutic interventions – studies performed at Botond Roska’s lab at the Friedrich Miescher Institute in Basel. “His drive to apply mathematical principles to neuroscience was contagious,” Siegert laughs, “and this was the time when I learned the programming language R and started to write my own scripts for analyzing my transcriptional data – a skill, I do not want to miss”.

Later during her post-doctoral work at Li-Huei Tsai’s lab at MIT, Siegert studied an epigenetic regulator associated with schizophrenia and its impact in memory formation. It was at the Boston environment, where she was exposed to the emerging impact of microglia interacting with neuronal function.

Microglia – one of the hottest topics of neuroscience

At ISTA, Siegert built an important research premise. “I realized that microglia were being artificially classified into reactive and non-reactive type with loosely defined subcategorizations. It was unclear to me which characteristics justify this taxonomy. Is it genetics, function, or morphology or some other?” She took up the challenge of setting up a baseline for microglia classification.

Microglia are cells that change their shape with their function. One of the very first questions Siegert asked at ISTA was whether cell morphology is a true indicator for separating the diverse microglia populations. “When we used traditional strategies to analyze microglia morphology it was not possible to distinguish microglia from different cortical regions or sex. Thus, we realized deriving their function without clearly defining the morphology will be challenging. Inspired by a presentation of applying principles of mathematical algebra to neuronal morphology, we developed a strategy that we named morphOMICS, which remarkably allowed us to identify differences in microglia morphology” Siegert says.

morphOMICS has been highly acclaimed in the field recently. And the Siegert group is only just getting started. Taking morphOMICS forward, her group is now focusing on answering fundamental questions like: Which functions do microglia have at a certain morphological state? How can we predict their interaction with neurons and which behavioral consequence does this have? And can certain stages be prevented to improve disease states? This approach has already led to many interesting findings.

Fighting depression with light

During the course of this work, the Siegert group made a startling discovery. In their experiments they found that microglia adapt their morphologies after being treated with ketamine. They identified that this enabled microglia to remove the perineuronal net, a structure that locks the brain in a functional state. This work is now being translated into an anti-depression strategy replacing ketamine with a non-invasive light therapy, which they showed to have a similar effect on the microglia. A new start up named Syntropic Medical GmbH that will prospectively offer this therapy has been founded with the support of xista.

Siegert explains that it has been more than 20 years of exciting scientific findings with several bold and risky decisions and at the same time being open-minded and curious that has led to the position she occupies today. “Looking back, I am amazed how I managed all the challenges along this path, and I only now start to slowly realize what I have achieved so far. I am excited now to enter a new chapter in my career. ”


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