Molecular Signaling Group
Head: Prof. Ivan Dikic
Research in the Dikic group is centered around the two major cellular quality control pathways: the ubiquitin system and autophagy. As such they provide protection against rapid aging and various human diseases and are involved in almost all cellular signaling processes.
Ubiquitin (Ub) is a highly conserved 76-amino acid polypeptide that is covalently attached to target proteins through a universally conserved three-step enzymatic process involving ubiquitin activating (E1), ubiquitin conjugating (E2) and ubiquitin ligating (E3) enzymes. Proteins can be modified by one (mono-ubiquitination) or several (multi-ubiquitination) single ubiquitin molecule(s). In addition, polyubiquitination of substrates occurs by the conjugation of ubiquitin proteins through one of its 7 lysine residues (K6, K11, K27, K29, K33, K48 and 63) or the N-terminal Methionine (M1) forming ubiquitin chains. Each type of Ub linkage is specifically recognised by specialised ubiquitin binding domains (UBD). To date, 20 families of UBDs have been characterized according to their specificity for Ub linkages (figure 1).
Given its high versatility, ubiquitination of proteins impacts almost all cellular pathways such as DNA repair, the immune response, endocytosis, autophagy, signaling and protein degradation (Hershko et al., 2000)
Figure 1: Ubiquitin binding domains recognise specific Ub linkages and have specialised functions. From Rajalingam and Dikic, 2016
Autophagy is a lysosome-mediated intracellular degradation pathway, which involves the formation of double-membrane vesicles (autophagosomes) that sequester portions of the cytoplasm or organelles and eventually fuse with the lysosome, where their cargo is degraded (figure 2). At first, autophagy was assumed to be a non-selective process to generate essential nutrients and building blocks required during cell starvation. However, during the last years, it became clear that autophagy is a tightly regulated, selective process that enables the specific degradation of damaged organelles, such as mitochondria (“mitophagy”), endoplasmic reticulum (“ER-phagy”) or invaded pathogens (“xenophagy”), maintaining cellular homeostasis.
Figure 2: Overview of selective autophagy. From (Stolz et al., 2014)
Prof. Ivan Dikic
Ivan was trained as a medical doctor in his hometown Zagreb (Croatia), before joining the lab of Joseph Schlessinger in New York in 1992 to pursue a PhD thesis in molecular biology. He moved back to Europe in 1997 to start his own group at the Ludwig Institute for Cancer Research in Uppsala (Sweden). In 2002, Ivan accepted a professorship at Goethe University and was appointed as director of the Institute of Biochemistry II in 2009. In parallel, he was the founding director of the Buchmann Institute for Molecular Life Sciences (BMLS), where he until today sustains an outstation lab. His research is dedicated to deciphering the molecular mechanisms of cellular signaling pathways, which have a high relevance to human diseases such as cancer, neurodegenerative disorders and inflammation. He was awarded with numerous recognitions, amongst them the Gottfried Wilhelm Leibniz Prize 2013 and election to the German National Academy of Sciences Leopoldina. Link to Director's page
Dr. Sagar Bhogaraju
Sagar obtained his master degree in Biological Sciences from Indian Institute of Technology, Kanpur, India. After a brief stint as a senior research analysis with a patent consultancy company Evalueserve, Delhi, he moved to Munich for his PhD at Max-Plank Institute for Biochemistry. He carried out his PhD under the supervision of Dr. Esben Lorentzen where he studied the structure and function of Intraflagellar transport proteins that are involved in making eukaryotic cilium. He later joined Ivan Dikic’s lab as a postdoc. He is interested mainly in structural and functional characterisation of ubiquitin ligases.
Dr. Florian Bonn
Florian studied biochemistry at the University of Greifswald. After graduating in 2009 he started his PhD studies also in Greifswald at the Institute for Microbiology in the labs of Michael Hecker and Dörte Becher. During his dissertation he investigated the antibiotic stress response of Staphylococcus aureus with gel-free proteomics. In addition, he worked as an LC-MS specialist in the institute and could gather experience with a wide range of mass spectrometers. Florian completed his PhD work in 2015 and after a short PostDoc in Greifswald he joined Ivan Dikics group in April 2016. As part of the SFB 1177 Florian is responsible for mass-spectrometry and assisting the group in development of new protocols for proteomic experiments.
Evgenij was born in Kaliningrad, Russia. He grew up in Germany and studied Biochemistry at the Free University Berlin, where he obtained his diploma degree. For his final thesis he joined the lab of Sven Diederichs at the German Cancer Research Center (DKFZ) in Heidelberg to explore the cellular response to DNA damage. To finish his diploma work he worked under the supervision of Lee Zou at Harvard Medical School in Boston. Driven by his interest in ubiquitin biology, Evgenij joined the Dikic group as a Boehringer Ingelheim PhD fellow and is currently working on the role of ubiquitin-modified proteins in the course of bacterial infections. In particular, he is investigating the function of novel cytoskeletal and inflammatory regulators during bacterial pathogenesis using a combination of high-accuracy mass-spectrometry, cell biological and biochemical approaches.
Dr. Paolo Grumati
Paolo was born in Vittorio Veneto (TV), Italy. He obtained his master degree in Medical Biotechnologies and his PhD in Genetic and Molecular Biology of Development at Padova University, Italy. Under the mentorship of Paolo Bonaldo, Paolo investigated the molecular mechanisms responsible for the muscular dystrophies linked to collagen VI absence. In particular he performed several studies in order to understand the role of autophagy in skeletal muscle homeostasis and disease. In October 2013 he joined Ivan Dikic's lab as post-doc and he is actually involved in a project aimed to better elucidate mechanisms of selective autophagy.
Marcel studied biology at the University of Giessen, Germany, to obtain his master degree with a focus on immunology and genetics in 2015. He did his master thesis at the Institute of Immunology, Giessen, where he investigated the Interleukin-1 receptor signaling complex. After a research internship in the lab of Henning Walczak, Cancer Institute University College London, Marcel joined the lab of Ivan Dikic as a PhD student. During his PhD he is working on cytokine signaling pathways and inflammation response.
Dr. Sissy Kalayil
Sissy did her Master’s in the Dept. of Biological Sciences and Bioengineering at IIT Kanpur, India. Following this, she spent almost two years in the Dept. of Biological Sciences at Vanderbilt University, Nashville, TN. Sissy obtained her PhD in Dec 2015 from the group of Prof. Dr. Werner Kühlbrandt at the Max Planck Institute for Biophysics in Frankfurt where she investigated the structural and functional aspects of membrane transporters. She joined the Dikic lab as a postdoc in Jan 2016 where she is trying to understand the properties of membrane curving proteins and also investigating the structural and biochemical aspects of novel ubiquitination mechanisms.
Dr. Lina Herhaus
After high school Lina obtained her first lab work experience in Mexico at the Research centre ECOSUR in San Cristóbal de las Casas. She then decided to study Applied Biology at Hochschule Bonn-Rhein-Sieg (Germany) and Molecular Biology at the University of Dundee (UK) where she obtained a double degree with Honours. Lina performed her PhD studies at the MRC Protein Phosphorylation and Ubiquitylation Unit in Dundee under the supervision of Gopal Sapkota. Her dissertation focused on how deubiquitylating enzymes regulate the TGF-beta and BMP signaling pathways. Lina is now an EMBO fellow in the lab of Ivan Dikic in Frankfurt (Germany), where she will investigate the role of ubiquitylation on tumor-stroma crosstalk.
Yaobin obtained his master degree in Pharmacology at Soochow University, China. Under the mentorship of Guoqiang Xu, he studied the mechanism by which Lenalidomide treats the blood cancer multiple myeloma. He joined the lab of Ivan Dikic as a PhD student in May 2016. During his PhD he is now working on the indentification of the activity and substrates of Legionella effector.
Dr. Jaime Lopez-Mosqueda
Jaime was born and raised in Los Angeles, California. He obtained his Bachelor's degree from the California State University, Northridge. Jaime then ventured to Northern California where he obtained his Ph.D. from the University of California, San Francisco. Under the mentorship of David Toczyski, Jaime's dissertation focused on how DNA replication is regulated during adverse conditions. He is now an EMBO fellow in the lab of Ivan Dikic in Frankfurt, Germany. Jaime is currently investigating the role of Wrnip1 and ubiquitin signaling in DNA metabolism.
Dr. Timurs Maculins
Timurs was born in Riga, Latvia, where he studied medicine in Riga Stradiņš Medical University. He has joint academic research via a Master of Science degree at the Erasmus Medical Centre Rotterdam with the support of the Huygens Scholarship awarded by the Netherlands Organization for International Cooperation in Higher Education. Timurs pursued his interests in fundamental research by joining the laboratory of Karim Labib at the Manchester Cancer Research Centre in the United Kingdom after receiving a doctoral studentship from Cancer Research UK. Using the budding yeast as a model organism in his doctoral work, Timurs studied a role of a novel enzyme, known as SCFDia2 ubiquitin ligase, during DNA replication in the S phase of the cell cycle. Tim’s most significant discovery is an observation that cells lacking SCFDia2 accumulate ‘un-disassembled’ replication complexes at the end of S phase, which is rescued by re-expression of the ligase. This constitutes a key step of a fundamental mechanism, known as replisome disassembly, which Timurs and his colleagues co-discovered in eukaryotes.
Timurs continued his career as a postdoctoral scientist in the pharmaceutical industry in a collaborative project between the AstraZeneca High-Throughput Screening Centre and the academic laboratory headed by Ronald Hay. Following his interests in ubiquitin drug discovery, Timurs developed a novel approach for modulating the activity of mammalian ubiquitin ligases with chemical compounds. This field of drug discovery holds a great therapeutic potential, but in the absence of reliable screening technologies remains largely unexplored. Working in close collaboration with Hay’s laboratory, Timurs has developed a robust method for pharmacological inhibition of ubiquitin ligases in mammalian cells and utilized it to discover small molecule inhibitors against Rnf8 enzyme that regulates DNA damage response.
In late 2015 Timurs joined a collaborative project between the laboratory headed by Ivan Dikic and Fraunhofer IME for developing innovative approaches for pharmacological targeting of the ubiquitin system. Most recently, Timurs has received the Human Frontier Science Program postdoctoral fellowship, which he will utilize for studying the role played by ubiquitin ligase-like effectors during infection by lethal bacterial pathogens.
Dr. Hadir Marei
Hadir was born in Cairo, Egypt. She obtained her Bachelor’s degree in Biology with a minor in Chemistry at the American University in Cairo. During her Bachelor’s degree, she also participated in an Erasmus exchange program, where she conducted her third year at the University of St. Andrews, Scotland. Following her Bachelor’s, Hadir was awarded a Cancer Research UK studentship to conduct a four-year PhD program at the Cancer Research UK Manchester Institute (CRUKMI) in the Cell Signalling group headed by Angeliki Malliri. During her PhD, Hadir was focused on dissecting the molecular mechanisms involved in dictating the biological outcomes mediated by the small GTPase Rac1, a key regulator of cytoskeletal rearrangements and cell migration. Stemming from her interest in small GTPases, Hadir joined the Dikic group as a postdoctoral fellow, where she is currently investigating the role of regulators of Rab GTPases in modulating autophagy. Additionally, she is also exploring the interplay between cytoskeletal regulators and the trafficking machinery, under normal and pathological conditions. Given her scientific background, Hadir is also interested in identifying novel proteins that modulate the cytoskeleton, particularly following bacterial infection.
After graduating from school, Masuda was trained as a medical technical assistent (MTA) at Klinikum Frankfurt Höchst followed by two semester studies of Bioprocess Engineering at the Frankfurt University of Applied Science. Since 2006 she is part of IBC2 and currently works as a technical assistant in the Dikic group.
Dr. Véronique Schaeffer
Véronique did her PhD in joint supervision between the University of Basel (Switzerland) and the University of Strasbourg (France) investigating the role of endogenous neurosteroids in the regulation of neurodegenerative processes. Afterwards, Véronique worked in the group of Michel Goedert (MRC - Laboratory of Molecular Biology, Cambridge, UK) where she has developed and characterized a transgenic mouse model of TDP-43 proteionopathy. She also conducted another project investigating the effect of autophagy stimulation on neurodegeneration in a mouse model of tauopathy. Véronique is now doing a second postdoc in the lab of Ivan Dikic where she intends to investigate further autophagic pathways.
Marta Seczynska studied biotechnology at the Jagiellonian University in Krakow, Poland, where she obtained her master’s degree in 2015. For the diploma thesis, she joined Department of Medical Biotechnology where she was investigating how heme oxygenase 1 affects biology of muscle progenitor cells and muscle tumorigenesis. During her master degree, for summer training, she joined laboratory of prof. David Holden at Imperial College London where she was involved in collaborative project between prof. Steve Ley and prof. David Holden concerning host signaling pathways during Salmonella infection. Marta is now PhD student in the lab of Prof. Ivan Dikic, where she is focused on understanding how ER contributes to the regulation of innate immunity and cellular stress response pathways.
Dr. Alexandra Stolz
Alexandra received her PhD under supervision of Dieter H. Wolf in the Institute of Biochemistry in Stuttgart, Germany, working on the identification and characterization of new players of endoplasmic reticulum associated protein degradation (ERAD). She started at IBCII in the Protein Engineering Group of Andreas Ernst in September 2013 focusing on the development of peptide-based ATG8 sensors. In 2015 she joined the lab of Ivan Dikic for functional validation of the beforehand engineered sensors in mitophagy and xenophagy. Alexandra is now working on the selective degradation of the endoplasmic reticulum (ER-phagy) with focus on the FAM134 family.
Head: Prof. Ivan Dikic
Institute of Biochemistry II
University Hospital Frankfurt
Theodor-Stern-Kai 7 / Building 75
60590 Frankfurt am Main
Lab 1 Tel: +49 (0) 69 6301 4862
Lab 2 Tel: +49 (0) 69 6301 83752