Dr Roberta Cacioppo on shaping your scientific identity

We’re delighted to hear from Roberta Cacioppo (MRC Laboratory of Molecular Biology), whose work focuses on the mechanisms underlying the interplay between RNA Polymerase II (RNAPII) homeostasis and gene expression control, which is fundamentally hijacked in cancer. Roberta’s passion for molecular biology stems from the fascinating complexity of the cellular machineries that dictate life, health and disease, and indeed an important achievement was discovering the first mechanism of quality control of RNAPII that ensures proper gene expression.

In this spotlight, Roberta shares how stepping outside her comfort zones and acquiring entirely new sets of technical skills has shaped her career so far.

“I studied RNA processing during my PhD, but in my postdoc I instead implemented bespoke biochemical assays to study the clearance of defective RNAPII from chromatin, while establishing a high-resolution ChIP-seq method. Expanding my research to computational analysis was a big challenge, but luckily, I actively collaborated with peer bioinformaticians that helped develop custom scripts for analysing RNAPII gene positioning and the nascent transcriptome.

This experience reshaped my scientific direction and allowed me to widen the range of research questions I am now able to answer - it taught me that I don't have to be limited by my existing skill set. This didn't just strengthen my technical versatility; it solidified my identity as a scientist who builds bridges between disciplines and creates tools that elevate the work of the entire team. I now believe that an achievement isn't just about solving a single puzzle, it can also be realizing that no technical barrier is too large to overcome if you are willing to reach out, adapt, and learn.      

Presenting my final postdoctoral research on RNAPII regulation at the 94th Harden Conference generated critical and motivating feedback from the audience and inspired additional experiments to maximize the impact of the upcoming publication. I also engaged with multiple group leaders for what promises future fruitful collaborations. Participating in the career panel discussion was important for receiving strategic advice for successfully navigating my upcoming transition to running an independent lab.

The best piece of advice I have been given during my career is to be more passionate about the research question than the answers. Shifting the focus from defending a specific result to wanting to deeply understand a core problem is a powerful approach for several reasons. It kills the fear of being wrong: If an experimental approach to the problem fails, it is not a personal defeat; it is simply one less wrong turn on the way to the right destination. Being anchored to a specific method leaves you behind, while being anchored to the challenge ensures you will always find a way to pivot. When focusing on the question, feedback no longer feels like criticism, but it becomes a tool to sharpen your skills and get to the right perspective.  Before rushing to performing experiments, I always find it very useful to first take time to pause and ask if I understand what I am trying to solve. Give yourself the grace to explore, discard bad drafts, and ask dumb questions.”

Roberta will soon be moving to Italy to lead a research programme on the molecular mechanisms controlling gene expression in cancer. Her wet lab will combine multi-omics, molecular biology and biochemistry to understand how the interplay between transcription and RNA processing can drive cancer.

Dr Mark Hanson on piecing together an evolutionary puzzle

Mark Hanson, whose research investigates the evolution of host-microbe interactions, shared his story with us.

“The literature is full of examples of host-microbe interactions ranging from mutualism to pathogenic, and I think people are very comfortable with what these terms mean. My research happened upon an unexpected finding: things we call mutualists can become rather pathogenic depending on a single host immune effector. That is to say, a single gene, with a known mechanism of microbe control, swings a host-microbe interaction on a knife's edge between mutualism and pathogenic behaviour. This level of host effector-microbe specificity has been found at the level of genes and is greatly affected by common polymorphisms within host genes.”

A key achievement in Mark’s career was deciphering the evolution of the fruit fly gene Diptericin B (DptB) and the microbial mutualist Acetobacter:

“A very exciting project started by my former lab (Bruno Lemaitre's group at EPFL, Switzerland) happened to unlock a whole new dimension of thinking on how the host innate immune system combatted specific microbes. Another group had already found an intriguing interaction between one of these immune effectors (Diptericin A, in fact) and an ecological pathogen Providencia. We had found a strikingly strong interaction of the gene Drosocin and Enterobacter. But it wasn't clear whether these important and specific interactions were just chance: if you kept iterating over microbes and host genes, you'd of course find some interactions that were more potent than others.

That's when we stumbled on the importance of DptB in controlling Acetobacter, which was one of the two canonical "mutualists" of fruit flies. I had previously noted loss of the DptB gene in various fly species, including both tephritid and drosophilid fruit flies, and realised that this loss accompanied ecological shifts away from fruit-feeding. When we checked, the microbiome of fruits is dominated by Acetobacter, but species that shifted to ecologies lacking Acetobacter also lost their ancestral DptB genes. Putting two and two together, DptB is an effector evolved to control Acetobacter common in rotting fruits, and in the absence of Acetobacter, there's no longer selection to maintain DptB in the genome, so it ends up stochastically lost.

I'd found evidence that the effector-microbe specificity we were seeing was not just random chance given enough iterative testing, it was informed by an evolutionary logic: the host immune system evolves silver bullet effectors to control ecologically-relevant microbes. This sounds intuitive, but the prior logic was that these effector genes (antimicrobial peptides) were broad-acting and generic, and so there was no expectation they could somehow specifically target certain microbes so strongly.

This was a real exciting time in the lab, which culminated in a crowning paper in Science in 2023. (Hanson et al., 2023; Science).”

Mark’s research group (started in 2024 at the University of Exeter) now investigates the factors that explain within- and across-species differences in response to the same infections, with a focus on innate immune responses both for effectors, and pathway regulation.

“With support from a travel grant from the Biochemical Society I attended and chaired the immunity and symbiosis section of the European Drosophila Research Conference in 2026. It was an excellent opportunity to network with my peers, and one of the first such international conferences I attended as a new PI. I was able to present posters from my work both on immune effector evolution, but also my secret second life on scientific publishing reform (see Hanson et al., 2024; QSS). I'm a staunch advocate of publishing in non-profit and society-run journals (like the Biochemical Journal!), and this was a great chance to reach out to a community that often didn't think about such things.”