Jan Larsson Lab

Our research focuses on how a cell establish a balanced gene expression and how this information is transmitted in cell division. To answer these questions, we study two gene regulatory systems in fruit flies that recognise and regulate two specific chromosomes. Understanding how chromosomes and chromosome-specific regulatory mechanisms have evolved over millions of years is central to characterize the mechanisms that govern that our genome can co-ordinately express the right genes at the right time.

We have previously isolated a gene encoding the chromosome-specific protein Painting-of-Fourth (POF), which specifically binds to chromosome 4 in fruit flies. Until then, chromosome-specific proteins were only described linked to sex chromosomes, e.g., the X chromosome in humans and fruit flies. The POF protein and its binding to the 4th chromosome are controversial since POF mediates chromosome-specific regulation on a non-sex chromosome, thereby raising questions on chromosome integrity and evolution of chromosomes and chromosome-specific mechanisms. Our results suggest that chromosomes may have unique chromosome-specific functions that will affect epigenetic memory and these are the functions we focus on. We have described the binding of POF to chromosome 4 and we know which genes POF binds to. We now want to understand how POF and the dosage compensation system for the X chromosome can recognise genes chromosome-specific, how they can regulate the expression of these genes, and how these chromosome-specific systems evolve.

Our focus over the next few years is to identify which factors contribute to chromosome-specific protein/RNA complexes finding the right chromosome and binding to the right genes and sorting out the mechanisms that then allow these genes to be properly expressed. We also want to sort out the molecular mechanisms used to regulate an entire chromosome in a coordinated manner and how these mechanisms are linked to the correct distribution of the genome during cell division.

How cells regulate chromosomes specifically is linked to what happens when cells have too many or too few copies of a chromosome or part of a chromosome, aneuploidy. Although aneuploidy is negative, these changes are hallmark of cancer cells, which are known to accumulate chromosomal rearrangements. We try to identify the biological pathways leading to aneuploidy, the expression programs induced and how organisms manage aneuploidy.

With our research, we hope to answer questions about how epigenetic systems are recruited into specific chromosomes or regions, and how these systems evolve and function. The strength of our model is that it is unique, while at the same time most likely to show general principles.