In this meeting we bring together reesearchers that study DNA replication in the context of chromatin regulation, changes in cell fate and the process of malignant transformation.Excellent European speakers are combined with Dutch speakers with complementary expertise. There are openings for short talks and posterpresentations from young researchers based on abstracts. We expect a lively meeting in an important, fast developing field.

The microtubule cytoskeleton is regulated by a group of microtubule associated proteins that are specifically targeted to growing microtubule plus ends. These protein are called plus-end tracking proteins or +TIPs. The highly conserved autonomous +TIP family of End Binding (EB) proteins controls the recruitment of most other +TIPs to microtubule ends and is a central regulator at microtubule ends. The interaction of EBs with microtubules and its partners is regulated by posttranslational phosphorylation events to control the multiple different functions microtubules have in the cell. In budding yeast the EB family is represented by the single homologue Bim1. Interestingly, in a proteomics screen for Bim1/EB1 binding partners several protein kinases were uncovered. Many of the kinases or their complex partners contain structural features observed in known Bim1/EB1 partners suggesting that they could represent novel Bim1/EB1 partners phospho-regulating microtubule function. Preliminary analysis of several kinases has confirmed the surprising interaction with Bim1/EB1. In addition, colocalization of microtubule tips with several kinases could be observed, and finally in vitro a purified kinase complex could phosphorylate recombinant +TIPs. The aim of this research proposal is to unravel the mechanistic and functional link between the microtubule plus ends and the identified kinases in budding yeast. I will determine the molecular mechanisms responsible for the interaction by generating mutant yeast strains and using purified proteins in vitro. I will study the temporal and spatial regulation of the interactions by cell cycle controlled experiments and fluorescent microscopy techniques. I aim to understand the cellular role of the interactions by studying microtubule dynamics, cell morphology and any cellular processes the kinases have previously been linked to, using mutant cells. Finally, I will determine if there is a level of conservation in higher eukaryotes by probing the interaction between +TIPs and the identified kinases in mammalian cells.

This project aims to explore deep generative models to simulate immuno staining in breast tissue samples. In pathology, assessing specific biomarkers, through this staining, is of the utmost importance for a detailed diagnosis, but represents additional time and costs. What if we could generate this samples virtually? It would not only facilitate an efficient use of resources but also enhance diagnosis speed and accuracy, contributing to improved patient care, particularly in resourcelimited settings. In this sense, by leveraging both in-house and public datasets, this study aims to demonstrate the feasibility and efficacy of AI models for virtual staining.

The reliability and accuracy of artificial intelligence (AI) algorithms can degrade when such algorithms are applied to new, varied datasets — a common challenge known as “distribution shift”. For example, an AI model trained to detect tumors in MRI scans from a single hospital may not perform well on scans from another hospital. To address this issue, we aim to adapt the internal representations of “foundation models”, which are pre-trained on diverse data without specific labels. These adapted representations may allow us to partially mitigate distribution shift and boost the model’s performance in a broader environment.