Research in our lab focuses on the processes that regulate cellular morphogenesis and cell signaling and protein homeostasis. 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.

Using yeast we study processes such as cell differentiation in meiosis, where yeast cell are prone to assemble spores inside the boundaries of the original cell, or microtubule dynamics in nuclear migration processes in mating yeast cells. We also study the cellular response to external stimuli that are processed via MAP kinase signaling pathways and that lead to specific adaptations, or we investigate questions that relate to protein degradation, qualtiy control and homeostasis.

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 advanced microscopic imaging methods. We constantly seek to develop new 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) or new so-called fluorescent timer proteins (tandem fluorescent protein timer; tFT) and other fluorescence microscopy based techniques, and combine these imaging methods with genetic and genomic approaches and with high-content imaging platforms, in concert with statistical data analysis and mathematical modeling to explore the processes of interest.

Some more thought and links on our research you can also find here.

 

Background

My laboratory is working in two fields. First, we develop methods and tools for the scientific community, from software to new types of microscopes to methods for genomic engineering of model organisms. Second, we are investigating different biological questions, from cytoskeleton to protein homeostasis and quality control to vesicular transport, cell signaling and cell morphogenesis. All of these studies incorporate systemic approaches where we address our questions using methods from quantitative biology in combination with genetics, deterministic and stochastic simulations and new instrumentation. For many of these projects we collaborate with different groups in bioinformatics, developemtnal biology, physics etc. Sometimes we obtain our motivation for a specific project from the unique opportunity to try out a novel method that we developed, and sometimes our motivation is rationalized by a puzzling biological question or observation that then drives the investigation.

 

Selected Key Publications 2011-2015 (for a full list of the publications, go here)

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. Protein quality control at the inner nuclear membrane. Nature 2014;516:410–3.

Meitinger F, Khmelinskii A, Morlot S, Kurtulmus B, Palani S, Andres-Pons A, Hub B, Knop M, Charvin G, Pereira G. A memory system of negative polarity cues prevents replicative aging. Cell 2014;159:1056–69.

Theer P, Mongis C, Knop M. PSFj: know your fluorescence microscope. Nat Methods 2014;11:981–2.

Gibeaux R, Politi AZ, Nédélec F, Antony C, Knop M. Spindle pole body-anchored Kar3 drives the nucleus along microtubules from another nucleus in preparation for nuclear fusion during yeast karyogamy. Genes Dev 2013;27:335–49.

Dona E, Barry JD, Valentin G, Quirin C, Khmelinskii A, Kunze A, Durdu S, Newton LR, Fernandez-Minan A, Huber W, Knop M, Gilmour D. Directional tissue migration through a self-generated chemokine gradient. Nature 2013;503:285–9.

Khmelinskii A, Keller PJ, Bartosik A, Meurer M, Barry JD, Mardin BR, Kaufmann A, Trautmann S, Wachsmuth M, Pereira G, Huber W, Schiebel E, Knop, M. Tandem fluorescent protein timers for in vivo analysis of protein dynamics. Nat Biotechnol 2012;30:708–14.

Capoulade J, Hufnagel L, Wachsmuth M, Knop M. Quantitative fluorescence imaging of protein diffusion and interaction in living cells. Nat Biotechnol 2011;29:835–9.