Cancer is an extraordinarily diverse disease that affects our society globally; it hits people of all ages and genders. Because of its high mortality rate, it is responsible on average for one in six deaths, and it is the second most common cause of death, according to the World Health Organization [1]. During the last decade, new ways of stimulating the inherent ability of our immune system to efficiently attack tumors were found, which was distinguished by the Nobel Prize in Physiology and Medicine 2018 for James P. Allison and Tasuku Honjo. Currently, entirely new principles for cancer immunotherapy are on the rise, based on the inhibition of immune checkpoints on the surface of T-cells (e.g. PD-1, CTLA-4, LAG-3, etc.) or respective ligands on the cancer cells (e.g. PD-L1); and cross-linking of immune cells to target cancer cells by e.g. bispecific antibodies or engineered CAR T-cells. Still, the complexity of every individual cancer limits the efficacy of immunotherapy to a maximum of 20-40% of clinical patients [2]. Even if cancer genetics is correctly determined, complex and unique cancer ecosystems may prevent successful immunosurveillance. As the so-called cancer-immunity cycle – a set of processes the immune system does to eliminate cancer – is damaged in cancer patients, the task of immunotherapy is to repair the breaches in the immunity cycle, via ‘external’ support, either with mono- or combinational treatment. Thus, the main goal in the community is to achieve transformative treatment results for more patients, via better immune cancer phenotyping [3]. Nanosensor devices merged with biological species, e.g. cells or molecules of similar nanosize, offers a remarkable increase in biosensor sensitivity. Despite this success, nanobioelectronics is still underrepresented in the field of oncology. While the research area has addressed their potential applications in early cancer diagnosis less efforts have been dedicated to the therapy development and patients monitoring. In treatment monitoring, potential use cases are mostly limited by liquid biopsy, detection of circulating tumor cells or circulating tumor DNA. The recent works extend the borders of the silicon based nanosensor applications to the field of cancer immunology, i.e. contributing to the optimization of the novel CAR T cell immunotherapy for the prostate stem cell antigens as well as against fibroblasts activation proteins [4]. Here silicon nanowire field-effect transistors are used to pre-select targeting molecules for an adaptive CAR-T cell operation. Focusing on a library of seven variants of E5B9 peptide that is used as CAR targeting epitope, we performed multiplexed binding tests using nanosensor chips. The correlation of binding affinities and sensor sensitivities enabled a selection of candidates for the interaction between CAR and target modules. Furthermore, we demonstrate the ability to monitor the immunotherapeutic drugs in vivo, using the electronic platform. In conclusions, the research landscape in the last few years has shown encouraging signs for nanoelectronics to be better represented in cancer research in near future. In particular, this approach can open new routes to perform a complex combinatorial analysis using tiny electronic chips and simultaneously screening multiple biochemical species thus facilitating the transition from conventional medicine to precision medicine in clinical oncology. [1] “Cancer – fact sheet”, World Health Organization (website), Feb (2022). [2] P. Sharma, et al. Cell 168 (4), 707-723 (2017). [3] D.S. Chen, I. Mellman, Immunity 39(1), 1-10 (2013). [4] T.A. Nguyen-Le, et al. Biosensors and Bioelectronics 206, 15 114124, (2022). [5] T.A. Nguyen-Le, et al. Small Science 2400515, (2025). Research is supported by the European Research Council (ERC) in frames of a Consolidator Grant (ImmunoChip, 101045415)

The heart performs a vital function in circulating oxygen-rich blood and nutrients throughout the body. The core genetic program underlying heart development is largely conserved across metazoans, and aberrations to this process can result in congenital heart disease. While key transcription factors such as Gata5, Tbx5a, Hand2 are known to regulate cardiogenesis, their downstream gene networks and chromatin-level mechanisms remain unresolved. Using the zebrafish model organism, we integrate transcriptomics and epigenomics (ATAC-seq) to characterize the transcriptome and chromatin landscape during heart development. Our analyses revealed dynamic gene expression and chromatin rearrangements throughout different stages of heart morphogenesis, likely representing genetic regulatory hubs driving key events of heart development. Furthermore, the loss of cardiac transcription factors perturbs global chromatin accessibility, particularly at evolutionarily conserved non-coding regions, suggesting these as candidate enhancers involved in heart development. To elucidate the role of these enhancers in heart development and disease, we employ both experimental and computational approaches for discovery and functional validation in the zebrafish. Ultimately, we aim to define the contribution of the dynamic transcriptional regulatory landscape to heart development and identify novel elements (both genic and non-genic) associated with congenital heart disease.

Stephen J. Gould once famously asked: “Should the tape of life be replayed, would it produce similar living beings?”. This question may never get fully resolved, but recent technological developments allowed us to ask a similar question transposed to the context of cancer: “If we initiate tumor evolution in multiple similar cells, will the same phenotype emerge?”. To tackle this problem, we made use of organoid cell culture models that recapitulates native tumors with increasing fidelity, and expressed cellular barcodes that make it possible to study evolutionary processes with high resolution, to establish an experimental ex vivo platform to study tumorigenesis. Specifically, TP53-deficiency was engineered into primary human gastric organoids from healthy donors and several clonally derived replicate cultures were evolved for over two years. The cultures were extensively interrogated by DNA and single cell RNA sequencing, and cell barcoding was introduced to examine subclonal dynamics. We observed that several features of gastric tumor evolution could be replicated by prolonged ex vivo culturing, that selection was similar across replicates from the same culture and that cultures from different donors evolved similar malignant phenotypes. This suggests that tumor evolution is partly intrinsic to the tumor cells, without the influence of a complex microenvironment, and moreover that this process to some extent is predictable. By “restarting the tape of cancer” under different conditions, we may find a path forward that thwart malignant transformation.

The arbuscular mycorrhizal (AM) symbiosis between plants and beneficial soil fungi provides key benefits to plants: AM fungi help the host plant to take up essential mineral nutrients and water from the soil, thereby increasing crop yield by up to 30%. However, the symbiosis comes at a cost. In return for soil nutrients, plants allocate up to 20% of their photosynthetically assimilated carbon to the fungal partner. This symbiotic carbon transfer has a major impact not just on plant and fungal physiology, but also on the global carbon cycle. In this talk, I will provide an overview of our current knowledge on how assimilated carbon is transferred from plants to AM fungi. I will also present our current work, which aims to understand how carbon allocation to AM fungi is regulated by the plant and how we might be able to exploit these regulatory mechanisms to maximise the benefits of the mycorrhizal symbiosis for sustainable agriculture.

Proteins are fascinating biomolecules responsible for virtually every process in our cells. To carry out their functions, most proteins must adopt the correct three-dimensional shape through a process known as protein folding. In cells, this process can begin while the protein is still being synthesised on the ribosome, one of the most ancient and complex molecular machines. Proper folding is critical, as misfolding can lead to severe diseases, including neurodegenerative disorders such as Parkinson’s and Alzheimer’s. In our research, we use molecular dynamics simulations (“computational microscope”) enriched with experimental data from nuclear magnetic resonance spectroscopy (NMR) and cryogenic electron microscopy (cryo-EM) to provide new insights into cellular protein folding and how the ribosome shapes it. We structurally characterised the folding pathways by capturing the intermediates that emerge in co-translational folding, but are surprisingly absent in vitro. Thanks to recent advances in cryo-EM, the so-called “resolution revolution”, we now have access to structural snapshots of 66 ribosomes from a range of organisms and organelles. By combining these structures with models obtained through breakthroughs in machine learning, exemplified by AlphaFold, we can now start to explore the structural and sequence heterogeneity of ribosomes and their potential influence on protein co-translational folding. Specifically, we have focused on the ribosomal exit tunnel, a long conduit through which the nascent polypeptides reach the outside of the ribosome. To analyse the geometric features of ribosomal exit tunnels in various structures, we have developed a computational method based on the nascent chain molecular dynamics simulations. With this approach, we characterised the nascent chain pathways in the tunnel and how they change between species and at different stages of biosynthesis. We also performed an extensive bioinformatics analysis of the sequences of proteins forming this ribosome tunnel to comprehensively describe ribosome heterogeneity and investigate the link between the ribosome and the proteome it synthesises.