Assistant professor in Molecular Biology
My group’s research focuses 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 represents a finely tuned equilibrium between protein production, maintenance, and degradation that is crucial for cellular well-being. At its core, the protein quality control (PQC) system, coordinated by a network of chaperones (the cellular chaperome), actively maintains this balance. It ensures proper protein folding and prevents the accumulation of misfolded proteins, thereby safeguarding cellular health. When proteostasis disruptions exceed the capacity of the PQC system, it leads to toxic protein aggregations with non-native conformations. Prolonged or chronic stress can upset this balance, resulting in proteostasis breakdown, cellular toxicity, and ultimately cell death.
Ageing is associated with the accumulation of intracellular damage, which compromises the functional proteome and leads to cellular dysfunction. As organisms age, maintaining proteostasis becomes increasingly challenging, contributing to the development of diseases such as cancer and neurodegenerative disorders. Given the unprecedented ageing of our population, coinciding with a surge in age-related diseases like neurodegenerative disorders, it is essential to uncover the changes in the ageing chaperome, including the structure and vulnerabilities of organellar PQC subsystems. We strongly believe that these insights will provide the foundation for future interventions in translational medicine.
We hypothesise that age significantly affects various aspects of organellar PQC. Impaired intracellular communication is a hallmark of ageing, and we expect disruption of communication pathways between suborganellar PQC with advancing age. Our research focuses on molecular details underlying the age-related decline of proteostasis and intracellular communication using high-throughput approaches in yeast, with the ultimate goal of validating and translating these findings into higher eukaryotic model systems.
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
I am the course leader for “Cell biology” (5MO100/3MB038) targeted at Bachelor’s students of Life Science and Biomedicine