Open Doctoral Positions 2021
last updated: 22.09.2020
The funded projects below cover most areas of natural and life sciences from Cell and Developmental Biology, Epigenetics, Genetics, Microbiology, Molecular Biology, Biochemistry, Evolutionary Biology, Plant Sciences, Pharmacology, and Systematics.
Should you have any inquiries about the funded projects below, please do not hesitate to contact the PI in charge of the project.
More info about the LSM faculty members´research could be viewed here
Prof. Dr. Claude Becker (Genetics)
Title: Genetic variation in rice momilactone biosynthesis
Plants mostly grow in dense communities, together with plants from the same or a different species. Because resources are scarce, plants must compete with their neighbours for nutrients, space, and water. In a strategy called ‘allelopathy’, plants produce and release chemical compounds that are harmful for their neighbours. This type of biochemical interference between plants also occurs between crop plants and weeds that infest agricultural areas.
Every year, weed infestation of rice fields, particularly by the grassy weed Echinochloa crus-galli (cockspur grass) causes massive losses in potential production. Rice is an allelopathic crop, meaning that it has the capacity to produce and release weed-suppressive chemical compounds. While momilactone A is produced when the rice plant is under attack by fungal pathogens, momilactone B is produced as a repellent against neighbouring weeds. However, it remains unclear how the rice plants perceive and recognize their neighbours. To develop allelopathy-based breeding strategies, knowledge on the natural genetic variation that determines the allelopathic strength of different rice strains is indispensable. In this project, we will use an existing resource of rice natural and cultivated variation, the 3000 Rice Genomes resource, to investigate the genetic components of momilactone production and its regulation. By combining metabolite analyses in hundreds of rice cultivars with genomic and quantitative genetic approaches, we aim to identify genomic loci that control the baseline production rate and the responsiveness to nearby neighbours of momilactone synthesis.
Prof. Dr. Nicolas Gompel (Cell/Evolutionary Biology)
Title: Regulatory evolution underlying quantitative pigmentation changes in Drosophila
The diversity of animal forms results from changes in shape, changes in size, as well as the emergence of new characters. The genetic origin of these evolutionary changes begins to be well understood. There is, however, another level of morphological diversification that remains much less understood, the quantitative variation of characters, such as the continuous range of colors or hues that decorate animals. With this project, we propose to use the different shades of gray that ornate the wings of fruit flies species closely related to the model organism Drosophila melanogaster, to address this problem. Leveraging the power of Drosophila genetics, the project will examine how the regulation of a pigmentation gene is tuned between species to produce this variation in pigmentation intensity.
We are looking for a PhD candidate to lead this project, combining molecular biology, Drosophila genetics, and quantitative image analysis. Our research group is located at the Biozentrum of the Ludwig Maximilian University (LMU) in Munich. With an international and interdisciplinary team, we train students to become full-fledge geneticists with a strong emphasis on quantitative approaches.
Expected candidate background:
The successful candidate is expected to have a strong theoretical background in Developmental Biology, Genetics and Molecular Biology. Practical experience with Drosophila genetics or molecular biology is an asset but not necessary for this position. Similarly, the ability to code in Matlab, Python or R is desirable but not mandatory to apply.
Prof. Dr. Peter Geigenberger (Plant Sciences)
Title: Role of thioredoxins and regulation of starch metabolism in acclimation of plants to low temperature
Low temperature is an important factor for plant performance. A decrease to sub-freezing temperatures leads to ice-formation and dehydration resulting in severe cellular damage. Acclimation of plants to low temperatures has been found to increase the freezing tolerance of temperate plant species, which is accompanied by a stimulation of photosynthesis and accumulation of soluble sugars. In our previous work, we found that the chloroplast thiol-redox system and downstream stromal metabolism are both crucial mediators for cold acclimation and freezing tolerance in Arabidopsis plants. The aim of this project is to analyze the mechanisms underlying these responses in detail by using reverse genetics and omics approaches.
Prof. Dr. Kirsten Jung (Microbiology)
Title: External electron carriers structure the landscape of interacting human intestinal bacteria
Bacterial growth is influenced by a wide variety of low-molecular compounds, which are taken up, released, or used for communication. These compounds are excreted as part of an overflow metabolism or are end-products or are produced with the purpose of communication or are released by lysed eukaryotic cells. There are recent findings on cross-feeding of e.g, quinones and GABA, by the human gut bacteria (Fenn et al., 2017; Strandwitz et al., 2019). External metabolites, such as pyruvate, do not only improve the fitness of bacteria, but are also important for the resuscitation of dormant cells (Vilhena et al., 2018, 2019).
In this project we will analyze how external electron carriers, e.g. protoporphyrine, influence community behavior and structure in physically separated bacteria. Biofilms are the preferred living form of bacteria, and therefore we will follow spatial arrangement of cells in biofilms, but also in microcolonies in time-lapse experiments. In addition, the molecular details of uptake, membrane integration and functioning of protoporphyrines shall be studied.
D'Souza, G., Shitut, S., Preussger, D., Yousif, G., Waschina, S., and Kost, C. (2018). Ecology and evolution of metabolic cross-feeding interactions in bacteria. Nat Prod Rep 35, 455-488.
Fenn, K., Strandwitz, P., Stewart, E.J., Dimise, E., Rubin, S., Gurubacharya, S., Clardy, J., and Lewis, K. (2017). Quinones are growth factors for the human gut microbiota. Microbiome 5, 161.
Strandwitz, P., Kim, K.H., Terekhova, D., Liu, J.K., Sharma, A., Levering, J., McDonald, D., Dietrich, D., Ramadhar, T.R., Lekbua, A., Mroue, N., Liston, C., Stewart, E.J., Dubin, M.J., Zengler, K., Knight, R., Gilbert, J.A., Clardy, J., and Lewis, K. (2019). GABA-modulating bacteria of the human gut microbiota. Nat Microbiol 4, 396-403.
Vilhena, C., Kaganovitch, E., Grünberger, A., Motz, M., Forné, I., Kohlheyer, D., Jung, K. (2019) Importance of pyruvate sensing and transport for the resuscitation of viable but nonculturable Escherichia coli K-12. J. Bacteriol. 201, e00610-18.
Vilhena,C., Kaganovitch, E., Shin, J.Y., Grünberger, A., Behr, S., Kristoficova, I., Brameyer, S., Kohlheyer, D., Jung, K. (2018) A single cell view of the BtsSR/YpdAB pyruvate sensing network in Escherichia coli and its biological relevance. J. Bacteriol. 200, e00536-17.
Prof. Dr. Dario Leister (Plant Sciences)
Title: Enhancing acclimation in plants
In this project, acclimation of plants will be enhanced by changing the expression of key factors of acclimation. These key factors have been already identified by systems biology approaches and additional ones will be identified in this project. A complementary approach to be used is based on adaptive laboratory evolution of photosynthetic microbes. Here, mutations in proteins have been identified that make the microbes tolerant to stresses. These mutated proteins will be also introduced into plants and tested for their impact on acclimation.
Prof. Dr. Stylianos Michalakis (epigenetics, neuroscience, bioinformatics)
Title: Role of TET-mediated 5mC oxidation for neuronal function
(Approval for funding is pending)
Scientific background: Neuronal networks show a remarkable degree of plasticity during physiological and pathophysiological processes. This plasticity goes along with major adjustments in the expression of key genes. The mechanisms controlling gene expression and neuronal plasticity are not well understood, but it is suggested that epigenetic mechanisms such as DNA methylation contribute crucially to these biological processes. Methylation of the DNA base cytosine is catalyzed by DNA methyltransferases (DNMT) and occurs at the C-5 position of the cytosine base resulting in 5-methylcytosine (5mC). Removal of the methyl group involves oxidation by TET methylcytosine dioxygenases. The overarching goal of this project is to help improving our understanding on how TET enzymes and 5mC oxidation products shape the epigenome of neurons and influence CNS function.
Specific aims and methodology. The functional role of TET enzymes in mouse brain and retina has not been fully investigated, and it will be addressed in this project. Using a combination of in vivo and in vitro models (2D neuronal cultures and 3D retinal organoids) we aim at elucidating the role of TET enzymes and their enzymatic products in neuronal differentiation and maturation. The expression level of TET3 enzyme will be manipulated using a variety of techniques in the above-mentioned models, and the effects will be analysed by the student in this project. TET enzymes act in concert with chromatin remodeling proteins and transcription factors. We identified intriguing novel TET interaction partners in mouse retina, mouse brain and/or induced pluripotent stem cell (iPSC)-derived neurons. The potential of these proteins, as well as the identification of novel interactors, to engage with the TET3 isoform and modulate its enzymatic activity will be assessed in this proposal. We are looking for a highly motivated PhD candidate with bioinformatic, genetic and epigenetic background and strong interest in neuroscience. The candidate will apply bioinformatic methods and will also have the chance to learn and apply genetic, biochemical, molecular and viral gene transfer methods in vitro and in vivo.
Further information and selected literature.
M. Wagner, J. Steinbacher, T. F. Kraus, S. Michalakis, B. Hackner, T. Pfaffeneder, A. Perera, M. Müller, A. Giese, H. A. Kretzschmar, T. Carell, Angew Chem Int Ed 2015, 54, 12511-12514.
A. Perera, D. Eisen, M. Wagner, S. K. Laube, A. F. Künzel, S. Koch, J. Steinbacher, E. Schulze, V. Splith, N. Mittermeier, M. Müller, M. Biel, T. Carell, S. Michalakis, Cell Rep 2015, 11, 283-294.
T. Pfaffeneder, F. Spada, M. Wagner, C. Brandmayr, S. K. Laube, D. Eisen, M. Truss, J. Steinbacher, B. Hackner, O. Kotljarova, D. Schuermann, S. Michalakis, O. Kosmatchev, S. Schiesser, B. Steigenberger, N. Raddaoui, G. Kashiwazaki, U. Müller, C. G. Spruijt, M. Vermeulen, H. Leonhardt, P. Schar, M. Müller, T. Carell, Nat Chem Biol 2014, 10, 574-581
Dr. Tamara Mikeladze Dvali (Cell Biology)
Title: Molecular Mechanisms regulating centrosome assembly and stability
Centrosomes are the major microtubule organizing centers of animal cells. Centrosome components have diverse functions in many different cell biological processes, ranging from cell division to cell polarity and signaling. Deregulation of centrosomal components can lead to human conditions as cancer and microcephaly.
Therefore, our research is focused on deciphering molecular mechanisms regulating centrosome dynamics in a living organism. In the recent years the centrosome has emerged a highly structured and dynamic organelle. It comprises a pair of centrioles surrounded by layers of pericentriolar material (PCM). In nonmitotic cells the PCM forms a thin layer (core) around the centrioles. When cells enter mitosis the PCM dramatically expands into a spherical mitotic centrosome, facilitating microtubule nucleation. SPD-5 (the functional homologue of the human microcephaly-linked protein, CDK5RAP2), SPD-2 (human Cep192) and the Polo-like-kinase-1, PLK-1 are part of an evolutionary conserved module driving mitotic PCM dynamics. In C.elegans SPD-5 is the main PCM matrix protein. It forms the non-mitotic PCM core and expands during mitosis in a SPD-2 and PLK-1-dependnet manner, providing the basis for robust microtubule nucleation and the formation of a bipolar spindle. Recently we identified a novel centrosomal protein PCMD-1 and demonstrated that PCMD-1 regulates dynamics of the SPD-5/SPD-2/PLK-1-module at the centrosome. In particular, in absence of PCMD-1 function targeting of SPD-5 to the non-mitotic centrosome core is abolished. As a result the integrity of the SPD-5-containing centrosome matrix at mitosis is severely compromised and the formation of a bipolar spindle is disrupted. However, how exactly PCMD-1 regulates centrosome
matrix stability and robustness remains an open question. We offer a PhD project, which builds on our current knowledge of PCMD-1 function. The aim is to dissect details of PCMD-1 interaction with centrosomal matrix proteins
and cell cycle regulators. The proposed project will use a variety of state of the art microscopy approaches, genetic and biochemical techniques in the nematode C.elegans.
Erpf AC., Stenzel L., & Mikeladze-Dvali T. PCMD-1 organizes centrosome matrix assembly in C. elegans. Current Biology 29, 1324–1336 (2019).
Woodruff JB., Wueseke O., & Hyman AA. Regulated assembly of a supramolecular centrosome scaffold in vitro. Science 348, 808–812 (2015).
Woodruff JB., Ferreira Gomes B., & Hyman AA. The centrosome is a selective condensate that nucleates microtubules by concentrating tubulin. Cell 169, 1066–1077 (2017).
PD Dr. Dejana Mokranjac (Cell Biology/Biochemistry)
Title: Molecular mechanisms of biogenesis of mitochondria
Mitochondria are fascinating cell organelles that not only produce most of ATP our cells need but are also key to initiating apoptosis. Though mitochondria contain their own genome, the vast majority of mitochondrial proteins are encoded in the nuclear genome. Thus, the proper structure and function of mitochondria critically depend on import of over 1000 different proteins that are synthesized on cytosolic ribosomes as precursor proteins and need to be transported to the correct mitochondrial subcompartment in order to reach the final place where they fulfil their biological function. About 70% of mitochondrial proteins use an N-terminal presequence as a mitochondrial targeting signal and are translocated with the help of the TOM and TIM23 complexes in the outer and inner mitochondrial membranes, respectively. The presequence pathway is used by essentially all matrix proteins, a large number of inner membrane proteins and even some intermembrane space- and outer membrane proteins. Translocation of proteins along the presequence pathway requires two energy sources – the membrane potential across the inner membrane and ATP in the matrix. The TOM and TIM23 complexes are highly complex molecular machines that consist of ca. 20 highly evolutionary conserved proteins, the majority of which are essential for cell viability. We are fascinated by the versatility of this pathway and the rich biochemistry behind it. By combining biochemistry, cell biology and yeast genetics, we aim to obtain a mechanistic understanding of the processes that enable recognition and translocation of proteins along the presequence pathway.
The project currently available in the lab will focus on elucidation of the molecular mechanisms of cooperation of the TOM and TIM23 complexes that enable coordinated translocation of proteins across two mitochondrial membranes.
To join us, you should have fun in doing basic research and preferably have previous experience in protein biochemistry and/or yeast genetics.
Project 1: Sequence adaptations in the symbiosis receptor-like kinase (SymRK) enabeling nitrogen-fixing root nodule development
Plant root symbioses with arbuscular mycorrhiza (AM) fungi and nitrogen-fixing bacteria bear huge potential for sustainable agriculture by reducing the chemical fertilizer input required to maintain high crop yields. The regulation and signal transduction mechanism leading to AM and the nitrogen-fixing root nodule symbiosis (RNS) share a genetic toolkit largely conserved across land plants. It contains a set of signal transduction components including the Symbiosis Receptor-like Kinase SymRK. During evolution, SymRK appears to have acquired novel molecular features that facilitated the development of the nitrogen-fixing root nodule symbiosis, while maintaining its conserved function for AM. In this project, we will explore sequence diversity among SymRK orthologs and paralogs with the goal to narrow down and identify critical sequence adaptations that underlie the rhizobial infection of plant cells. The doctoral student will investigate the mechanistic consequences of these adaptations at the cell biological and biochemical level with a focus on interacting proteins. The relevance of SYMRK paralogs and interacting proteins will be explored by reverse genetics utilizing transposon insertion populations or CRISPR/CAS genome editing technology and quantitative binding studies in vivo using advanced light microscopy and in vitro using a range of state-of-the-art technologies. We expect novel insights into the molecular mechanisms facilitating the symbiotic infection process of plant cells by nitrogen fixing bacteria.
Project 2: Spatio-temporal dynamics in the composition and function of the CCaMK/CYCLOPS complex
Plant root symbioses with arbuscular mycorrhiza (AM) fungi and nitrogen-fixing bacteria bear huge potential for sustainable agriculture by reducing the chemical fertilizer input required to maintain high crop yields. The regulation and signal transduction mechanism leading to AM and the nitrogen-fixing root nodule symbiosis (RNS) share common components including the calcium and calmodulin dependent protein kinase (CCaMK) and its phosphorylation target CYCLOPS, a DNA binding transcriptional activator (Tirichine et al., 2006; Yano et al., 2008; Singh et al., 2014). The CCaMK/CYCLOPS complex is a central regulatory hub in symbiosis signaling. It controls the expression of three transcriptional regulators of three distinct developmental programs. NIN controls nodule organogenesis and, together with ERN1, infection thread formation while RAM1 is indispensable for arbuscule development (Singh et al., 2014; Pimprikar et al., 2016; Cerri et al., 2017). The corresponding promoters control distinct timing, expression domains and response to different stimuli. The promoter choice and activity of CCaMK/CYCLOPS must therefore be coordinated at a spatio-temporal and a stimulus-specific level to trigger appropriate cell developmental programs. In the past, we identified additional putative complex components that may contribute to binding of diverse cis regulatory elements within the known target promoters of CCaMK/CYCLOPS. The doctoral student will study the relevance of the identified additional complex components using a range of techniques, including reverse genetics utilizing transposon insertion populations or CRISPR/CAS genome editing technology. The spatio-temporal composition of the complex and its structural rearrangement will be studied via in vivo FRET-FLIM in root hair nuclei in response to signals emanating from arbuscular mycorrhiza fungi or nitrogen-fixing bacteria. Biochemical in vitro measurements will be used to quantify protein-protein and protein-DNA binding affinities. We expect to unravel key steps in the molecular dynamics of the CCaMK/CYCLOPS complex underlying the specific activation of the appropriate and distinct developmental programs in response to fungi and bacteria and thus the establishment of AM and root nodule symbioses.
Project 1: Tackling multi-host pathogenicity of Xylella
Disease epidemics represent a critical threat for crops and increase global concerns about food security and social stability. Xylella fastidiosa is a bacterium transmitted exclusively by sap-sucking insects that feed on xylem fluid. The bacterium is spreading across Europe, threatening olive production. The EU-funded (ERC) MultiX project aims to reduce disease in crops without yield losses. We will use a multi-host method combined with dual transcriptomics to systematically analyse bacterial and plant signatures related to disease caused by X. fastidiosa in four plant species and two bacterial isolates. The specific goal of the PhD project is to reveal bacterial virulence gene functions of selected differentially expressed genes by genetic manipulation and phenotype characterization in multiple host plants. At the completion of this project, we will identify the molecules contributing to multi-host pathogenicity that, when targeted, could mediate infection control of X. fastidiosa.
(Funded by ERC Adv Grant)
Project 2: The role of bacterial extracellular RNAs in plant infections with Xylella
Extracellular vesicles (EVs) are important bacterial structures, which have been associated with infection success of Xylella fastidiosa (Xf). This PhD project will evaluate the role of XfEVs in host infection and is part of the DFG-funded national research unit RU5116. Given that EVs could transport bacterial extracellular RNA (exRNA) species, our specific goal is to identify the EV RNA repertoire associated with Xf disease and to address the modulation of plant’s immune system by EV RNAs. We will also contribute to comparative studies within the RU5116 and develop molecules interfering with bacterial infection. Together, this project will lead to new insights into cross-kingdom RNA exchange controlling Xylella’s infection success.
(Funded by DFG Grant)
Prof. Dr. Korbinian Schneeberger (Computational Genetics)
Title: Infection-induced mutation rates
In this project, we will study the impact of pathogen infection on mutation rates within the model plant species Arabidopsis thaliana. Upon infection, plants show increased DNA repair action, which suggests that pathogen infections also increase DNA damage and thus increase mutation rates – both within the plant, but also in the offspring of the plant. Intriguingly, the elevated DNA repair activity is specific to selected regions of the genome including the regions that encode resistance genes against the pathogens. This leads to the fascinating hypothesis that plants increase mutation rates in resistance genes to increase the genetic diversity in their offspring, which we can now test. Using A. thaliana lines, which have been grown for 15 generations with and without pathogen infections will be compared for their differences in the mutational spectra und frequencies and will allow us to gain insight in one of the most fundamental prerequisites of evolution: mutations.