In our #NextGen Signalling Scientists series, we spotlight Early Career Researchers who are shaping the future of signalling research at CIBSS.

This feature highlights molecular biologist Dr. Tanja Bhuiyan, independent postdoc at the Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, in the groups of Prof. Dr. Sebastian Arnold  and Prof. Dr. Robert Grosse.

In this interview, Tanja Bhuiyan talks about her journey into academia and what drives her curiosity. She explains her latest research findings, which were recently published in Cell Reports (Bhuiyan et al. TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors. Cell Reports, Vol. 44, Issue 5, 2025. DOI: 10.1016/j.celrep.2025.115616).

For more info on the paper see the press release here.

Tanja, your recent study highlights how spatial organisation within the cell nucleus connects transcription and RNA processing — what fascinates you most about this dynamic interplay and what’s exciting about your findings?

Tanja Bhuiyan: In our study, we found that spatial organisation in the cell nucleus helps coordinate transcription and RNA splicing — two core processes of gene expression that are more tightly linked than previously thought. Transcription and RNA processing are essential steps in gene expression. In Eukaryotes, most splicing occurs while transcription is still ongoing, with the elongating RNA polymerase interacting with splicing factors. We found that transcription factors involved in the earliest phase – initiation – can bind to splicing factors. Surprisingly, this coupling is influenced by nuclear speckles – compartments without any DNA or polymerase activity. Nuclear speckles were first described over a century ago by Santiago Ramon y Cajal, long before the rise of Molecular Biology as a discipline. In the past, gene transcription was seen as a step-by-step process with proteins binding in sequence. This view has shifted: we now understand gene regulation as a dynamic process. For example, the basal transcription factor TFIID contains flexible, so-called intrinsically disordered regions which can form liquid-like condensates that help organise nuclear processes.

TFIID is a key transcription complex that helps initiate gene transcription by binding to DNA. Interestingly, one part of this complex – TAF2 – can detach and form so-called condensates, which are dense, droplet-like structures inside the nucleus. TAF2 then localises to nuclear speckles, specialised areas involved in RNA processing. In speckles, TAF2 interacts with RNA-binding proteins and splicing regulators. This suggests that TAF2 might help coordinate transcription with RNA splicing. We were especially surprised to see a link to alternative splicing – the process that allows a single gene to produce different mRNA variants. It shows that proteins involved in gene regulation can take on unexpected functions.

Did your project reveal any unexpected findings or did it spark new questions in the areas of cellular organisation and gene regulation that you would like to explore further?

Tanja Bhuiyan: I clearly remember the most surprising moment during this study: it was the instant at the microscope when I realised that TAF2 condensates are nuclear speckles. What may seem obvious in hindsight wasn’t at that time and it challenged my assumptions. This was a vivid reminder that scientific discovery often happens beyond our anticipation. My original hypothesis was that the entire transcription complex TFIID forms condensates on DNA, similar to RNA polymerase II as shown in previous studies. But it soon became clear that only one subunit – TAF2 – efficiently forms such condensates. At first, I assumed they were DNA-associated, but that assumption turned out to be wrong. This also illustrates the scientific writing process: the sequence of events in the lab does not necessarily correlate with the sequence of the final figures in a paper. Our first data came from mass spectrometry, which showed that TAF2 interacts with many RNA-binding proteins and splicing factors. At the time, such proteins were often dismissed as contaminants. But after a deeper look into the data and lots of reading I decided to test their localisation with the help of nuclear markers. Using the nuclear speckle marker sc35, I saw that TAF2 perfectly localised to speckles – that was unexpected and a rare moment of treasure. As Pasteur said, “luck favors the prepared mind” – without all that analysing and reading, I wouldn’t have been able to let my old assumptions go and conceive this experiment.

These questions point to broader challenges in the field, such as investigating how regulatory mechanisms are organised in space and time, and how their disruption leads to disease. Genetic mutations in key regulatory processes often cause severe phenotypes during early embryonic development or neurodevelopmental stages. The reason why these basic mechanisms are especially important during neurodevelopment still remains unclear. Another major question is how different molecular processes – like transcription and splicing – are coordinated. We still know surprisingly little about the mechanisms of co-transcriptional splicing or the roles of many RNA-binding proteins involved. Visualising these events at the surface of nuclear speckles could offer valuable new insights.

What drives you personally to keep investigating how cells coordinate complex molecular processes — and where do you hope this knowledge could make a difference in the future?

Tanja Bhuiyan: I have always been curious, loved exploring the unknown and figuring out how nature and especially life works. As many children of immigrants in Germany, I grew up with a low socioeconomic status and I certainly did not picture myself as a scientist. I hardly knew anybody with a university degree and had no scientific role models. Nevertheless, I decided to study Biology. Science isn’t a solo effort, the people around us shape our path. I was lucky to have a great PhD mentor, Winship Herr, who inspired me and introduced me to the world of gene regulation. Complex molecular processes are the key to life and studying them satisfies my curiosity. You don’t need to feel predestined for a career in research. What matters is passion, creativity, and a unique point of view – and that’s why diversity enriches scientific discovery. Passion is essential, but so is a supportive environment. We need to keep up those efforts toward an even more inclusive academic environment, where researchers from all backgrounds can realise their full potential.

Creating such an environment is crucial, as it fosters the kind of diverse perspectives that are essential to tackling some of the biggest questions in biology. One of the questions that fascinates me most is how genes and environment interact. Genes determine less than we used to think. In complex organisms like humans, control is decentralised and distributed across many levels and agents.

There is evidence that gene regulation networks that go awry underlie complex neurodevelopmental disorders. Understanding how cells regulate genes will hopefully contribute to disease prevention and to the development of therapeutics in the future.