Prof. Michaela Müller-McNicoll

by Paula Petronela Groza

Dr. Michaela Müller-McNicoll, a professor at the Institute for Cell Biology and Neuroscience, Goethe-University Frankfurt/Main, Germany. She is also one of the currently elected Directors of RNA Society (2022-2024 term). Dr. Müller-McNicoll researches “the role of RNA in subcellular compartmentalization and how changes in subcellular architecture under stress affect mRNA processing and export”. Together with her team, they “develop new methods and apply RNA biochemistry, ribonomics, cell biology and bioinformatics to study different aspects of subcellular compartmentalization”. They re-evaluate “aspects of splicing and gene regulation that we do not understand from a subcellular compartmentalization perspective”. Particularly, they focus on “how hypoxia stress or SUMOylation changes subnuclear architecture to regulate alternative splicing and hypoxia adaption in cancer and endothelial cells.”

She “got hooked on RNA during her Master’s and PhD theses” which focused on “regulation of gene expression in Leishmania, which occurs exclusively post-transcriptionally and involves cis-acting sequences within the 3' UTRs of mRNAs”. Afterwards, she “completely switched system and topic for her postdoc and joined the lab of Prof. Karla Neugebauer”. This transition was not easy - “coming from an organism that does not support pre-mRNA splicing”, she “could really not wrap her mind around this complicated process”.  Thus, she started to work on studying the role of “SR proteins in post-splicing steps in gene expression, while teaching splicing to undergrads and getting more comfortable to study alternative splicing as well”. During this time, SRSF7 became her favourite protein/transcript because, “it is full of surprises and is so fascinating and versatile and contains an ultra-conserved poison exon. Dependent on its alternative splicing and polyadenylation isoforms it can act as an mRNA, a Split-ORF transcript, a long non-coding RNA or even an architectural RNA that assembles nuclear bodies.”

Shortly after her post-doc, she became a junior professor at the Institute for Cell Biology and Neuroscience, Goethe-University Frankfurt/Main, Germany. Six years later, in 2020, she was promoted to full professor at the same institution. The transition from junior rofessor to her current position was marked by an important advice from her “PI mentor and friend Prof. Michael Feldbrügge,” which pushed her to “stop giving postdoc talks”. She recalls that “as postdoc and young PI” she “used to give talks that tell one cool story, but they were always heavy on data. As an experimental biologist she always wanted to show everything that she did including nitty gritty details and controls so that everyone believed her and followed her arguments. The wealth of cool data made her feel comfortable, but often got her audience lost.” Gaining more experience as PI, she became more confident and trusted more in her research capabilities which also reflected in her talks: “It was time to change, not showing all experiments and all data points, only selected data that support the conclusion, think more and about bigger problems, present more concepts and questions, present two or three stories that go together and provide a bigger picture, don’t lose your audience with nitty gritty details.” This helped her “to better communicate” her research program. As she progressed in her career, her vision also expanded and improved. Thus, she is currently transitioning her lab “from studying SR proteins to studying this fascinating process (subcellular compartmentalization) from many different angles including the role of SR proteins”. This change was influenced by her two idols Joan Steitz and Lynne Maquat, who told her “Don’t study a protein – study a process.”

Dr. Müller-McNicoll is involved in other aspects of the scientific community which have a more administrative nature, as well. Although she finds these types of tasks challenging, she is aware that “If you hesitate, you will lose”. These words came from her postdoc adviser and friend Prof. Karla Neugebauer and serve as encouragement to “take on jobs that seem way too big” but which allow her to grow.

“Think more about bigger problems, present more concepts and questions…, provide a bigger picture and don’t lose your audience with nitty gritty details.”

Whenever she feels stuck, she reminds herself about a phrase she heard at her first Cold Spring Harbor Laboratories conference: “If you don’t know what to do anymore - look in the microscope” and “this is what I do - I look at RNA in the microscope and it is absolutely fascinating what we have already learned from this.” The pandemic has impacted Dr. Michaela’s career and has been “the biggest challenge in my career so far” and made her feel like she must “start all over”. Moreover, she observed that the careers of female scientists were much more affected by the pandemic. “In 2019/20 my career was finally rising - I was invited for seminars, published cool stories, and finally got talks at conferences. But then COVID-19 hit, and my energy, productivity and visibility sank to an all-time low. At home I was balancing childcare (1-year-old) and home schooling (11-year-old). At work I was desperately trying keep my group together per Zoom. I was only on emergency brain mode but had no time to think and advance science. This was certainly the situation for many researchers with small kids, but it affected female researchers more. It hit me when I participated in a grant evaluation panel last week and out of 95 applicants, and only 7 were women.” Despite these struggles, her work is also sprinkled with joy. Prof. Dr. Müller-McNicoll confesses that her biggest achievement to date is the success of her PhD students: “I am very proud of the achievements of my first batch of PhD students. They set up the lab, established all techniques and protocols that we needed and made discoveries for the years to come”. She recalls joyfully that “A few months ago, we reunited, and they gave me a really nice gift and told me how much they appreciate the training and the independence they got in my group and how it made them thrive in their new jobs. That made me really happy.”

As for her recipe for success, she thinks that “from my perspective it seems to me that successful young PIs develop new methods, apply it on interesting biological systems and combine it with molecular simulations/artificial intelligence/mathematical modelling. This allows them to ask and answer important biological questions for which each subject alone is not sufficient anymore”.

The RNA Society and the broader scientific community around it is “very precious” to Dr. Müller-McNicoll, because her work “is very much centered around RNA-protein interactions without focusing on a particular disease, model system or step in gene expression, I have only this one RNA community”. She considers the RNA Society “very inclusive and provides a home, a community, a sense of belonging to its members” which gave her very pleasant memories. The most memorable one took place during the RNA Society meeting 2017, where she attended with her four PhD students who were at the time not “convinced that their work mattered”. The Keynote presentation that Prof. Adrian Krainer delivered that year describing his lab’s splicing research and the development of Spinraza completely changed her students’ perspective and turned out to be “an emotional, proud and wonderful moment” for her group. This talk “tremendously boosted our motivation to study the complicated ways how SR proteins regulate splicing and connected processing steps”.

Her favourite article in the RNA Journal is “Evidence for reassociation of RNA-binding proteins after cell lysis: implications for the interpretation of immunoprecipitation analyses by Mili S, Steitz JA” because it showed her for the first time “that one can also publish negative results” and made her use “exclusively UV-crosslinking techniques to detect or quantify RNA-protein interactions that occur in intact cells”.

You can find Prof. Dr. Michaela Müller-McNicoll on Twitter @mixmue or  her lab’s website.