Simone Mayer: Deep insights into the development of the mammalian neocortex

The Hertie Institute for Clinical Brain Research together with the Neurology Hospital of the University of Tübingen forms the Center of Neurology focuses on the research, treatment and teaching of human brain diseases. Dr. Simone Mayer is an independent research group leader at the Hertie Institute. Her lab is studying how neurotransmitters modulate mammalian cortical development, evolution and disease emergence. As a part of Neuromag’s “Meeting a Scientist” program, GTC doctoral student Harshad P.A. asked Simone Mayer about her current research and future plans.

What is the exact focus of your research?      

I work on the development of the mammalian neocortex. I am especially interested in this brain region, since it is a hallmark of us, mammals, and has expanded significantly in mammalian evolution, especially in the human lineage.

Therefore, I think that knowing the physiology of the neocortex will provide us with a better understanding of the basis of our cognitive abilities and also what goes wrong in diverse disorders that have emerged in our species. In my lab, we focus on the development of the neocortex, especially on the time period in which neural stem and progenitor cells generate diverse cell types, in the second trimester of gestation. Since we are interested in clinical conditions that are caused by problems during neocortical development, we preferentially use human neural stem cell models such as cerebral organoids.

Neuroectodermal tissue embedded in Matrigel droplet at day 11 of the cerebral organoids protocol (Lancaster and Knoblich, 2014). The scale bar in the image is 200 µm (picture was taken by Kseniia Sarieva, Mayer lab).

Why is it important to do research on your topic?    

Recently, the Zika epidemic has attracted attention to the field of developmental neurobiology.  Within a few months, thousands of babies with brain defects were born in Brazil after the mothers were infected with a novel strain of the Zika virus during pregnancy. Based on basic research in the field of brain development, following the outbreak of Zika-virus-induced microcephaly in Brazil, several research groups quickly showed which cell types in the developing brain were attacked by the virus and revealed which molecular pathways activated by the virus could be drug targets. The Zika epidemic thus highlighted the importance of basic research on the cellular and molecular mechanisms of human brain development and how they can be compromised to cause disease.

What outstanding techniques do you employ at your lab? 

I was a postdoc at the University of California, San Francisco before I came to Tübingen. It was a very exciting time with the single-cell RNA sequencing (scRNA-seq) field really taking off and one its main centers was in the Bay Area. In my postdoc lab, my colleagues and I used scRNA-seq approaches in many different projects ranging from basic biology (creating an atlas of cells in the developing human neocortex) to physiology (combining calcium imaging with scRNA-seq) and disease applications (for example autism and multiple sclerosis). I aim to establish the technology and the mindset of studying the brain at single-cell resolution in my lab.

What has motivated you to come to Tübingen?        

Tübingen is a hotspot for clinical neuroscience research and especially the Hertie Institute offers excellent conditions to work at the interface between basic biology and clinical questions. In the past months, I could also already connect with other researchers interested in brain development during pregnancy and beyond from a clinical or psychiatry perspective in Tübingen. This has led to the launch of our Neuro Campus Initiative “The Developing Brain” which I’m very excited about. From a methodological point of view, the strength of Tübingen in sequencing, bioinformatics, and data science is also an advantage for my work since it allows collaboration to analyze data more deeply and comprehensively. I am looking forward to exploring how we can integrate with the Cyber Valley in the years to come.

What is your opinion about the value of collaboration in science?

Since I started my career in science about a decade ago, I have seen the increasing importance of collaboration. Nowadays, most papers in my field have many authors from several different research groups, since different perspectives and methodological strengths are required for generating new knowledge and putting together a comprehensive “story”. I already know many colleagues with complementary skills and interests in Tübingen and I think that we can make some great discoveries together. The Tübingen Neuro Campus Initiative is a great motor for internal collaborations. In the context of brain development, I have launched the Neuro Campus Initiative “The Developing Brain” where we aim to provide a forum of exchange on this topic in Tübingen. I would like to invite everyone interested in the developing brain to join our seminars (happening every 3 months) or contact me directly.

What are your ideas for the future? What do you hope to achieve in Tübingen? What are your immediate and long-term goals?

My main goal for the future is to determine the molecular mechanisms that link defects in brain development during pregnancy with behavioral outcomes using both environmental exposure as well as genetically determined disorders as model systems. As I am setting up my lab, my immediate goal is to establish a lab culture where students and postdocs can learn to become independent thinkers. This is important because critically assessing the literature and our colleagues’ work is key to identifying the most promising new research directions. However, critical thinking skills are in my opinion not only important to be a good scientist, but also a crucial skill beyond academia. In the era of fake news and with populism rising, we need to be able to assess the evidence for different positions in all domains of life. As scientists, I see it as our responsibility to promote evidence-based decision-making in the society more broadly.

Finally, as a successful female scientist, what advice would you like to share with other emerging female scientists?

It is hard to give a general statement of advice. Instead, I will share a few strategies that have helped me along the way. To start with, for me it has been extremely helpful to have role models and mentors to seek advice from. I am extremely grateful to the supportive scientists I have met along the way. Each person gives advice based on their own history, so it has to be taken with a grain of salt. In moments of doubt and hesitation, I have focused on my big goals and dreams. Finally, having a supportive partner has made a huge difference, especially when moving to new countries and faced with the challenge of building up a professional and personal life more or less from scratch. 

The interview was conducted by Harshad P.A. He is currently a GTC doctoral student at the Hertie Institute for Clinical Brain Research in the Experimental Epileptology Group of Prof. Dr. Holger Lerche.


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