• understand mechanisms of stress response
• discover short- and long‐term consequences of cellular responses and their crosstalk in physiology
• apply the gained knowledge about stress responses for the development of new medical treatments.

Prof. Chacińska will seek to identify global consequences of translational inhibition in human cells. Preliminary data show that although acute stress leads to rapid inhibition of protein synthesis, this stress is not lethal and frequently cells become even more resistant to further insults. Unknown adaptive mechanisms lead to re-initiation of protein translation. Prof. Chacińska’s group will undertake a system analysis of gene expression changes that accompany dysfunctional mitochondria, aiming to identify changes in transcription various steps of mRNA biogenesis and stability, including splicing – in collaboration with the Konarska lab – as well as translation activity/recruitment of mRNA during translation initiation. Studies of the group will deliver a comprehensive gene expression profiling under mitochondrial dysfunction and will lead to a discovery of yet unknown responses and adaptive pathways that have a potential to rescue cells and organisms from organellar stress and may in general benefit cellular and organismal fitness.

Prof. Konarska group will study the mechanisms by which aging or environmental signals influence the function of the splicing machinery and affect splicing outcomes. Changes in patterns of alternative splicing in higher eukaryotes are characteristic signatures of stress and disease, but little is known about the underlying mechanisms. These studies will help to understand how environmental changes or ageing affect regulation of gene expression at the splicing level. They will also help to understand the function of the spliceosome and suggest new ways to modulate it. Ultimately, the mechanisms utilized by yeast to regulate pre-mRNA splicing will also be validated in mammalian cells, and the way how they affect more complex regulation of alternative splicing will be studied in collaboration with the Chacińska group.