Research of the Lindeboom lab
The Lindeboom lab uses quantitative biology to understand how cells maintain their identity and interact with the immune system. A linchpin in our lab is our aim to measure exact copy numbers, binding- and turnover-rates within the proteome, transcriptome and epigenome, which enables us to build quantitive models to explain the behaviour of cancer cells and their recognition by immune cells.
T cells can recognize diseased cells such as cancer cells through specific interactions between specific T cell receptors and antigens that are presented on cancer cells. However, both healthy and cancer cells can potentially present millions of different antigens, while only few of these will specific and abundant enough to distinguish cancer from healthy cells. We therefore use mass spectrometry-based absolute proteomics, degradomics and immunopeptidomics to measure the absolute expression levels and turn-over rates that determine highly abundant antigen presentation. Complementary to this, we use single cell genomics approaches to characterize and identify the T cells that can recognize cancer antigens.
In addition to modeling proteome dynamics and antigen presentation, we also study the relation between absolute abundances of (oncogenic) proteins and their regulatory function. Many oncogenes are also present in healthy cells as proto-oncogenes where they execute essential processes while their abundance is tightly controlled. In cancer, the elevated expression through for example genomic amplifications gives new functionalities to these proteins that contribute to the formation of cancer. We aim to understand how a DNA binding protein can activate different pathways at different levels of expression. To this end, we continue to develop tools such as BANC-seq (Neikes et al., 2022, https://www.biorxiv.org/content/10.1101/2022.04.04.486948v1.full) to measure the impact of protein concentration on epigenome-wide binding. By combining epigenome profiling and BANC-seq we can measure and predict how changes in protein concentration can lead to new binding sites and subsequent gene regulation, and how epigenetic alterations in cancer affect this.