Current Projects

"Anti-Aging" Hormone Klotho

When the ectodomain of the membrane protein "Klotho" is enzymatically cleaved, Klotho circulates as "anti-aging" hormone in blood circuit. In mice lacking Klotho an accelerated aging can be observed. Already at young age, they show age-related symptoms, such as osteoporosis, atherosclerosis, deposition of calcium e.g. in the arterial wall or loss of fatty tissue – all of them usually occuring only in very old animals. In contrast, mice with an excess of Klotho live longer.

Also in humans, Klotho was shown to be linked to a prolonged lifespan and improved cognitive abilities. Produced in the kidney and brain, it is responsible for several (hormonal) regulation processes. In mouse models, we try to find how Klotho prevents aging and which role it plays in the brain. To this end, we genetically inactivate Klotho in different tissues and analyze changes in behavior, lifespan and physique of our mice.

Rer1, a new type of retrieval receptor

One of the most important functions of endoplasmic reticulum (ER) is to guarantee the trafficking of correctly folded protein complexes. We recently identified a mammalian retrieval receptor, Rer1, that transports escaped proteins back from the cis-Golgi to the ER. What’s special about Rer1 is that it recognizes sorting signals in transmembrane domains and is responsible only for specific membrane protein complexes, which not all are yet known. We want to study the molecular details of transmembrane domain mediated sorting and the role of Rer1 therein.

Notch in Neurons

The Notch receptor is essential for development, but also involved in learning and memory. However, it’s also known that its hyper activation leads to carcinogenesis. We study where and how in neurons Notch is processed and how the signal transduction is mediated. Moreover, we found notch-inhibitors which we try to deeply understand in order to improve their effect.

Furthermore, we conducted a high-throughput screening of chemical compounds and the human genome to find compounds and further proteins involved in the notch signal transduction. One of the identified compounds in which we are currently interested is FLI-06. FLI-06 inhibits the protein export from ER, targeting an unknown mechanism which we want to identify.