Ruprecht-Karls-Universität Heidelberg

Michael Knop
ZMBH Research Group Leader & DKFZ Group Leader

Im Neuenheimer Feld 282
69120 Heidelberg
Tel.: +49-6221 54 4213
Fax.: +49-6221 54 5893

Homepage at DKFZ

Lab Homepage

Welcome to the Knop Lab!

Systems biology, meiosis and signal transduction

Research in our lab focuses on the processes that regulate cellular morphogenesis and cell signaling. These are very active and rapidly evolving areas of research that are driven by work conducted with model organisms such as yeast, flies or worms. The studies provide important conceptual and experimental input into work conducted with medically relevant mammalian systems.

Cell differentiation processes are associated with cellular pathways that regulate structural functions and metabolic changes necessary that the cell can adopt its new role. Using yeast we study cell differentiation in meiosis, where yeast cell are prone to assemble spores inside the boundaries of the original cell. We also study the cellular response to external stimuli such as the yeast mating pheromone. This leads to stimulation of the cell via MAP kinase signaling pathways and to a polarization necessary for cell-to-cell fusion.

The small size of the yeast genome and the rich spectrum of available methods make this organism an ideal model system to decipher the machinery or the mechanistic principles behind these processes. The goal of our work is to obtain a systems-level understanding of the main molecular processes behind the regulatory as well as the structural aspects.

An important driver of our work is the ability to observe cellular processes by microscopic imaging methods, such as live cell imaging. Here we seek to continuously expand our methods in order to be able to image protein functions in more details. We use methods such as fluorescence cross-correlation spectroscopy (FCS/FCCS), fluorescence lifetime imaging (FLIM) and other so-called F-techniques, in order to obtain to information about bio-molecules and their interaction partners in their natural environment. We combine these functional high-content imaging methods with genetic and genomic approaches to explore the processes of interest.

We currently focus on the following areas:

1. We would like to understand the extent by which spatial partitioning of cells by reaction-diffusion mechanisms does contribute to the regulation of signal transduction processes.
2. We would like to understand the evolutionary dimension of molecular mechanisms. By comparing the situation in related species we can obtain insight into the constraints that shape particular processes.
3. We develop new approaches and microscopic methods in order to improve systemic studies towards the function of proteins within complex processes using novel high-content imaging or screening methods.

5 Selected Publications

Khmelinskii A, Blaszczak E, Pantazopoulou M, Fischer B, Omnus DJ, Le Dez G, Brossard A, Gunnarsson A, Barry JD, Meurer M, Kirrmaier D, Boone C, Huber W, Rabut G, Ljungdahl PO, Knop M. (2014) Protein quality control at the inner nuclear membrane. Nature 516: 410-413 (see Abstract)

Gibeaux, R, Politi, AZ, Nédélec, F, Antony, C & Knop M (2013) Spindle pole body-anchored Kar3 drives the nucleus along microtubules from another nucleus in preparation for nuclear fusion during yeast karyogamy. Genes. Dev. 27:335-349 (see Abstract)

Khmelinskii, A, Philipp J Keller, PJ, Bartosik, A, Meurer, M, Barry, JD, Mardin, BR, Kaufmann, A, Trautmann, A, Wachsmuth, M, Pereira, G, Huber, W, Schiebel, E & Knop M (2012) Tandem fluorescent protein timers for in vivo analysis of protein dynamics. Nat. Biotechnol. 30, 708-714 (see Abstract)

Capoulade, J, Wachsmuth, M, Hufnagel, L & Knop M (2011) Quantitative fluorescence imaging of protein diffusion and interaction in living cells. Nat. Biotechnol. 29, 835-839 (see Abstract)

Maeder CI, Hink MA, Kinkhabwala A, Mayr R, Bastiaens PIH*, Knop M* (2007) Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling. Nat Cell Biol 9(11): 1319-1326. *co-correspondence (see Abtract)