Image: Andreas Kohler
Image: Andreas Kohler
Research group We focus on high-throughput screening in simplified model organisms, combined with validation in higher systems, to understand human health and disease.
We base our research on high-throughput screening of microbial cells. The automation of our robotic handling system allows us to screen thousands of strains and conditions simultaneously, gaining a conceptual understanding of cellular mechanisms as a foundation for detailed investigations. With extensive expertise in yeast screening applications, we are eager to extend our repertoire to other microbial cells.
Proteostasis and ageing
Cellular proteostasis is the intricate, finely tuned balance of protein synthesis, maintenance, and degradation, essential for sustaining cellular health and linked to longevity. It continually faces challenges from unfolded proteins produced during biosynthesis, misfolding due to genetic errors, and damage caused by proteotoxic stressors. Chaperones and other protein quality control (PQC) factors are in place to facilitate proper protein folding and prevent the accumulation of abnormal misfolded proteins. While PQC systems typically maintain proteome integrity under normal conditions, aging reduces this capacity, contributing to various human diseases, including cancer and neurodegenerative disorders. Accumulating intracellular damage is a hallmark of aging, as the proteostasis network becomes burdened with increasing loads of misfolded and oxidatively damaged proteins. The decline in maintaining a functional proteome is a key driver of age-related cellular dysfunction and degenerative diseases.
With our research, we will enter novel grounds by studying the interplay of localized PQC systems and their change over different life stages and conditions, thus adding age and age-related disorders as additional complexity factor. Our research is based at the intersection point between data- and hypothesis-driven research, implementing powerful bioinformatic analyses to understand new aspects of PQC as one of the most fundamental processes of cellular life. We will combine the simplicity of yeast with the multifacetedness of human cell culture. Yeast's unique attributes, such as its remarkable adaptability, exceptionally short lifespan, and high interspecies conservation, render it an excellent model for investigating aging and proteostasis. Furthermore, the availability of multiple whole-genome libraries, which enable the straightforward identification of individual mutants through unique barcodes, enhances its suitability for high-throughput experiments. Our ultimate aim is to translate knowledge acquired from yeast research into a deeper understanding of the aging processes in human cells. Yeast acts as a valuable roadmap, helping us identify the critical pathways to explore, which we can then investigate within the intricate landscape of human cell culture.
Infection Biology
As a newly established UCMR member, driven by our motivation to go beyond state-of-the-art screening with yeast, my group is keen to complement infection-biology-based research questions with robotic high-content screening power to identify powerful intervention strategies and understand fundamental principles.
More information: www.vkohler-lab.com
Publications
IceLab opens its Lunch Pitch season with pitches related to aging from Verena Kohler and Mattias Forsell
