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CSC-LSM doctoral projects


Please note:

  • You have to apply through our online application tool which is open until 30 November 2022, 12:00 noon CET!
  • For further information about the projects, feel free to contact the supervisor directly
  • The offered projects of this CSC application cover most areas of natural and life sciences from Cell and Developmental Biology, Genetics, Evolutionary Biology, Plant Sciences, Pharmacology, Systematic Botany and Mycology.
  • On the online application tool, three projects can be selected.
  • You are welcome to browse through our faculty members´research here
  • APPLY NOW
Research groups

 

Title: Induction of defence compounds in rice by fungal elicitors
Project description:
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. Some plant species, including important crops such as rice, release chemical compounds to inhibit the growth of neighbours and to defend themselves against various pests.

Upon perceiving a chemical trigger, rice plants produce and release a particular type of diterpenes, momilactone A and B, that act against fungal pathogens as well as against non-kin plant species (Serra Serra et al. 2021). In this project, our goal is to identify the molecular trigger(s), the mechanism by which they are perceived, and the signalling cascade that ultimately leads to the enhanced production and release of the compounds. To this end, we employ a combination of genetics, genomics, biotechnology, and metabolomic analyses. In collaboration with microbiologists and biochemists, we will test an array of fungal extracts and filtrates from both beneficial and pathogenic fungi; via iterative fractionations and purifications, we aim to identify the specific molecules that trigger the response. Using reporter lines, mutant collections, and CRISPR/Cas9 technology, we will then focus on identifying the components of the signalling cascade.

The project is embedded in a group with very diverse expertise, ranging from Bioinformatics and Genomics to Plant Genetics and Biochemistry. We are looking for candidates with a solid background in molecular biology and genetics; expertise in computational data analysis and/or plant biology is a plus. Candidates should have an advanced level in spoken and written English.
For further information, please contact Dr. Claude Becker
Prof. Dr. Thorben Cordes (Physical and Synthetic Biology)
Title: ABC importers as targets for antibiotics of pathogenic bacteria
Collaborative Project: Kirsten Jung (Microbiology)

Description:
Multidrug resistant bacteria and lagging development of novel antibiotics were the cause of >17 million deaths in 2006.1 As pointed out by the world health organization (WHO) new strategies against drug resistant bacterial infections are urgently required (www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed). Bacterial ATP Binding Cassette (ABC) import systems have a huge potential as targets for antibiotic development due to their involvement in a numerous biological processes, their extracellular localization and the absence of homologous proteins in the mammalian hosts.2 These transmembrane systems transport wide variety of substrates ranging from sugars and peptides to metal ions, osmolytes and vitamins by utilizing the energy from ATP-hydrolysis. Different studies have shown that certain ABC importers are involved in bacterial virulence or survival in the host organism.2 Here, we propose to disable the periplasmic or extracellular components of ABC import systems, substrate binding domains or proteins (SBPs). They initiate substrate transport via its delivery to the membrane-embedded ABC import system allowing selective and ATP-coupled transport. In the framework of this project, you will conduct a structural analysis of the selected SBPs, establish and optimize the methods for protein expression, purification and fluorophore labelling of the target SBP and test the established fluorescence assays using single-molecule3, bulk- and high-throughput fluorescence detection methods. Furthermore, you will identify SBP inhibitors in silico, test and optimize their ability to bind the relevant SBPs in biochemical experiments. Finally, in collaboration with the lab of Kirsten Jung, you will test the impact of promising inhibitor molecules on the growth and infectivity of bacteria.
For more information visit our webpage

References:
1. Martens, E.; Demain, A. L., The antibiotic resistance crisis, with a focus on the United States. The Journal of antibiotics 2017, 70 (5), 520-526.
2. Garmory, H. S.; Titball, R. W., ATP-binding cassette transporters are targets for the development of antibacterial vaccines and therapies. Infection and immunity 2004, 72 (12), 6757-6763.
3. de Boer, M.; Gouridis, G.; Vietrov, R.; Begg, S. L.; Schuurman-Wolters, G. K.; Husada, F.; Eleftheriadis, N.; Poolman, B.; McDevitt, C. A.; Cordes, T., Conformational and dynamic plasticity in substrate-binding proteins underlies selective transport in ABC importers. eLife 2019, 8, e44652.

https://www.mikrobiologie.biologie.uni-muenchen.de/forschung/ag_cordes/index.html

 

Prof. Dr. Ferraz  (Biology of Reproduction)
Title: Creating a testis-on-a-chip to investigate the effects of microplastics on male fertility
Description
Reproduction is central to the capacity for species to maintain stable, healthy populations. Simply, if life can not reproduce, it will cease to exist. Over the past several decades, there has been a shift towards a “throw-away society” that is characterised by the excessive consumption of short-lived and single-use products, and a concomitant accumulation of environmental pollution and toxicants. Over this same timespan, there has been an alarming increase in the rates of reproductive dysfunctions and gamete abnormalities, reductions in gamete production, and altered embryo development in humans, animals and plants. This poor reproductive health not only reduces individual fecundity but, if widespread, species survival. While humans have introduced numerous pollutants that can impair reproductive systems, the potential impacts of microplastics (MPs) are of particular concern. Emerging studies are showing that MPs represent a potentially serious threat to the reproductive health of terrestrial species. Our lab has recently discovered the presence of MPs in seminal plasma and follicular fluid, and that MPs impact both female and male gametes in vitro.

To better understand the impact of MPs on male fertility, this project will combine bio-printing with microfluidics to develop an in vitro testis-on-a-chip model to study the effects of different microplastics particles on spermatogenesis and sperm function.

Please contact Prof. Ferraz for more information.

Dr. Sonja Grath (Evolutionary Biology/Ecology)
Title: O brother, where art thou? - Modelling the evolution of parthenogenesis

Description
We are generally interested in the evolution of genetic and epigenetic mechanisms that determine sex-specific gene regulation. Animals display a wide variety of reproductive modes. While sexual reproduction is widespread and well-known, with this project, we aim to better understand the evolution of reproductive modes where males are actually absent. We will use mathematical modelling to understand different forms of parthenogenesis. Under which circumstances can this form of reproduction evolve and be maintained? In arthropods, parthenogenesis can be induced by endosymbionts such as Wolbachia that can perform different reproductive manipulations on its hosts. One example is cytoplasmic incompatibility (CI) where Wolbachia manipulates the sperm of infected males. When mated with an uninfected female, or a female harboring a different and incompatible strain of Wolbachia, the manipulated sperm leads to partial or even complete incompatibility with the female's eggs and induces lethality of the offspring by disrupting the development of the embryo. If the female however does carry the same Wolbachia infection and Wolbachia is also present in her eggs, the manipulation can be rescued, allowing for viable offspring to be produced. Previously, we developed a mathematical model to study under which circumstances CI can spread between and maintained in populations of oak gallwasps. In this project, we now want to extend and generalize this model to additional species, parameters and reproductive manipulations.
Given a sincere interest in molecular and evolutionary mechanisms, the project is also well suited for graduates from disciplines outside biology, such as mathematics, physics or computer science. Just get in contact with the principal investigator in case you have any questions.
Contact information:
For further information, please contact Sonja Grath

Literature
van der Kooi, C. J., Matthey-Doret, C., Schwander, T. (2017). Evolution and comparative ecology of parthenogenesis in haplodiploid arthropods. Evolution Letters 1-6: 304–316. https://doi.org/10.1002/evl3.30
Werren, J. H., Baldo, L., & Clark, M. E. (2008). Wolbachia: master manipulators of invertebrate biology. Nat Rev Microbiol, 6(10), 741-751. https://doi.org/10.1038/nrmicro1969

Prof. Dr. Marc Gottschling (Systematic Botany and Mycology)
Title: Evolutionary origin and distribution of Bavarian freshwater dinoflagellates

Description:
Precise distribution data are necessary to explain the historical biogeography of organisms and to uncover the evolutionary mechanisms that have shaped their diversification, but also to predict future developments in a drastically changing world. The distribution of microorganisms, such as the ecologically and economically important group of unicellular dinophytes, reflects their dispersal ability and potential to establish new populations. Data on the distribution of these organisms, however, are both sparse and outdated. Molecular methods (including high throughput sequencing) have become the tool of choice to resolve identification issues. The successful candidate will inventory freshwater dinophyte species compositions of some 50 lakes in Bavaria, using rRNA amplicon sequencing. Bavaria has 382 lakes >1 ha that show a broad range of environmental parameters. Most lakes originated after the last ice age about 10-12.000 years ago. The group has multiple annual dinoflagellate morphology-based microscopic records (54 of them from research at the LMU Limnological Research Station Seeon). Phylogenies show that freshwater dinophytes segregate into distantly related lineages, and their molecular diversity is much better explored than their geographic occurrence. Dinophyte communities and their correlations with environmental parameters will be analysed with modern multivariate statistical methods, and the Bavarian ribotypes will be placed in a phylogenetic context using maximum likelihood methods. Bavarian dinoflagellates will also be considered in the European context using GenBank and the in-group sequence database of multiple spatially referenced accessions. The project will result in better knowledge about the spatial distribution and phylogenetic diversity of German dinophytes, will provide the first modern distribution maps for key species and is the basis for assessing the impact of climate change and acidification on freshwater dinophytes.

Selected publications
Gottschling M, J Chacón, A Žerdoner Čalasan, St Neuhaus, J Kretschmann, H Stibor & U John* (2020): Phylogenetic placement of environmental sequences using taxonomically reliable databases helps to rigorously assess dinophyte biodiversity in Bavarian lakes (Germany). Freshw Biol 65: 193–208.
Kretschmann J, A Žerdoner Čalasan, W-H Kusber & M Gottschling* (2018): Still curling after all these years: Glenodinium apiculatum Ehrenb. (Peridiniales, Dinophyceae) repeatedly found at its type locality in Berlin (Germany). Syst Biodivers 16: 200–209.
Žerdoner Čalasan A, J Kretschmann & M Gottschling* (2019): They are young, and they are many: Dating freshwater lineages in unicellular dinophytes. Environ Microbiol 21: 4125–4135.

 

 

Prof. Dr. Dr. Christian Grimm (Pharmacology and Toxicology)
Title: Novel endolysosomal transportome/channelome components in health and disease

Current State of Relevant Research

Cells are the elementary units of all life. Each cell contains numerous organelles that are essential for proper cell function, e.g. ribosomes for RNA into protein translation, a Golgi apparatus for protein modification, or mitochondria for energy production. One organellar machinery that is both essential for intracellular trafficking and degradation but also serves as an important signaling hub is the endolysosomal system. Endolysosomes are key for human health and disruption of endolysosomal function including its central role in intracellular Ca2+ signaling is strongly associated with disease pathology, affecting or causing neurodegenerative and lysosomal storage diseases, cancer and immunological diseases, metabolic, lung, or infectious diseases. The seemingly complex interaction between endolysosomes but also with other organelles raises the fundamental, yet largely unanswered question in cell biology of how a precise regulation of this intracellular communication and interaction network is achieved. Decoding the intracellular signaling pathways governing endolysosomal communication is critical not only for an in-depth understanding of cell biology
but also for the many disease pathologies endolysosomal dysfunction is associated with. Aim of this project is to decipher molecular components in mammalian cells that are necessary to tightly coordinate intracellular, in particular endolysosomal transport and communication, postulating that a distinctive set of endolysosomal cation channels/transport proteins are key to these processes. To address this aim, we will apply in vitro and in vivo models, novel techniques in cell biology, subcellular imaging, proteomics, bioinformatics and biophysics (i.e., endolysosomal patch clamp electrophysiology).

Peliminary Work Directly Relating to the Research Program
Members of the TRP family of mostly non-selective cation channels, the so called TRPML channels and the related two-pore channels (TPCs) which all reside in endolysosomes have been in depth investigated and characterized in the past. Yet, additional components of the endolysosomal transportome/channelome require further investigation, so do the numerous postulated interaction partners of TPCs and TRPMLs.

Specific Aims
Aims of the projects are
1) to characterize novel interaction partners of TPCs and TRPMLs in endolysosomes using endolysosomal patch-clamp electrophysiology and calcium imaging
2) to characterize additional components of the endolysosomal transportome/channelome
3) to identify novel, currently enigmatic components of the endolysosomal transportome/ Channelome

 

Prof. Dr. Heinrich Jung (Microbiology)
Title: Transport and regulation: The role of solute/sodium symporters in bacterial signal transduction

Description:

Transporters of the solute/sodium symporter (SSS) family transport sugars, amino acids, vitamins, and ions in cells of all domains of life. However, SSS proteins also form domains in prokaryotic signal transduction systems. The physiological significance and molecular mechanism of function of SSS domains in these systems are not known. Given that covalent binding between a transporter and a signal transduction system has emerged during evolution and has become widespread in the domain of bacteria, including Proteobacteria, this project focuses on elucidating the functional significance and underlying molecular mechanisms of the interactions between the SSS domain and signal transduction system. Using the sensor kinase/response regulator system MxtR/ErdR of the soil bacterium Pseudomonas putida KT2440 as a model, we test a possible direct control of signal transduction by the SSS domain of MxtR in response to ion gradients, membrane potential, binding and/or transport of a solute. Furthermore, we investigate the influence of other sensor kinase domains on a possible transport activity of the SSS domain in response to intracellular stimuli. We expect the results of this project to provide new insights into the function of SSS family proteins and a better understanding of the regulatory networks of P. putida KT2440. These findings may facilitate the use of the genetically accessible, solvent-resistant and safe bacterium as a platform for industrial biosynthesis (for example, plastic-like polymers, biosurfactants). Since homologs of the MxtR/ErdR system are also found in important pathogens such as Pseudomonas aeruginosa, we also expect to contribute to better understand the regulatory network of these bacteria.

Qualifications:
Experience with microbiological techniques, e.g., generation of mutants and reporter strains, and molecular and biochemical techniques, e.g., purification and characterization of proteins, is required.

References:
Henriquez, T. and Jung, H. (2021) Involvement of the MxtR/ErdR (CrbS/CrbR) two-component system in acetate metabolism in Pseudomonas putida KT2440. Microorganisms 9, 1558

Henriquez, T., Wirtz, L., Su, D., and Jung, H. (2021) Prokaryotic solute/sodium symporters: versatile functions and mechanisms of a transporter family. Int. J. Mol. Sci. 22, 1880

Wirtz, L., Eder, M., Schipper, K., Rohrer, S., and Jung, H. (2020) Transport and kinase activities of CbrA of Pseudomoinas putida KT2440. Sci. Rep. 10, 5400

 

Prof. Dr. David Keays (Developmental Neurobiology)
Title: Modelling TUBB2A Associated Disease States with Cerebral Organoids.

Description:

This project will provide mechanistic insight into human brain malformations caused by mutations in a beta-tubulin gene, TUBB2A, by exploiting advanced human stem cell-based methods.The human cerebral cortex is one of the most complex biological structures in biology. Its development involves a carefully orchestrated sequence of events that can be divided into three major stages: i) the generation of neurons; ii) the migration of neurons from their place of birth into the developing cerebral cortex; and iii) and the maturation and differentiation of neurons forming functional circuits.

Cortical development is dependent on correctly functioning microtubules: dynamic, scaffold-like polymers composed of alpha- & beta-tubulin heterodimers. Microtubules generate the intracellular forces required for each major stage of cortical development: i) they form the mitotic spindle during cell division, facilitating the separation of sister chromatids; ii) they enable translocation of the nucleus and extension of the leading process during neuronal migration; iii) and microtubules polymers extend and maintain large and longstanding axons in mature neurons that enable connectivity with often distant regions of the brain.
TUBB2A encodes for a beta-tubulin protein. Different TUBB2A variants give rise to a spectrum of cortical brain malformations including microcephaly (reduced brain size) and lissencephaly (smooth or broadly convoluted cortical folds). The specific cellular mechanisms underlying cortical malformations are poorly understood. We hypothesise that TUBB2A mutations affect the correct assembly, stability and/or the dynamics of microtubule polymers which, in turn, perturbs correct neuronal proliferation, migration and/or differentiation during cortical development.

This project will investigate TUBB2A-related disease using human stem cells. We have obtained skin fibroblasts from individuals with cortical malformations harbouring TUBB2A mutations and these have been reprogrammed to induced pluripotent stem cells (iPSCs). We have additionally used CRISPR/Cas9 to ‘repair’ patient mutations back to wild-type sequence, generating suitable control lines to pinpoint the mutation-specific effects on cortical development.

The project will involve differentiation of patient and control iPSCs into 2D neuronal cultures to determine the effects of TUBB2A variants on microtubule biology and function. Furthermore, to characterise potential consequences of TUBB2A mutations on neurogenesis, neuronal migration, and cortical organisation, we will use patient and control iPSCs to generate cerebral organoids, 3D neuronal cultures that recapitulate early stages of human cortical development.

Interested students should contact Professor Keays via e-mail

 

 Prof. Dr. Hans-Henning Kunz (Plant Sciences)
Title: Linking plastid ion transport and functionality

Description:

All cellular organisms tightly control their inner pH and ion composition to ensure proper function of vital biochemical reactions. In eukaryotes this includes several distinct sub-cellular compartments, adding further complexity to the system. Internal homeostasis is maintained via transport proteins embedded in the organellar membranes. Our group researches the chloroplast, an organelle of endosymbiotic origin and the site of eukaryotic photosynthesis.

In the model plant Arabidopsis thaliana, we have shown that the loss of two inner envelope (IE) membrane homologous K+/H+ antiporters (AtKEA1 and AtKEA2) affects organelle biogenesis and photosynthetic performance. Our recent studies suggest defects in rRNA maturation and plastid gene expression (PGE) as the main cause for the developmental effects but the mechanistic link between the function of plastid ion transporters and the intricate gene expression machinery in the stroma remains unclear.
It is possible that the lack of AtKEA1/2 in the plastid indirectly affects nucleic acid processing and maintenance due to global effects of aberrant ion composition and stromal pH. However, IE AtKEA proteins were shown to adopt a polar distribution in young dividing or developing plastids. Interestingly, in mature organelles the protein localization seems to change again but remains limited to distinct patches within the IE. Both pattern hint at a more direct role for IE KEAs in biogenesis centers or cell/organelle cycle control.
Within these microdomain-like spots, the antiporters may tightly regulate local pH and ion concentrations necessary for proper membrane formation and organization. Intriguingly, envelope-localized KEA carriers exhibit a large N-terminal stromal loop, which is required for the specific localization pattern. Additionally, the loop could enable IE KEA proteins to directly interact with nucleoid acids and/or other critical components of PGE.
To address these questions, we have escaped the complexity of multicellular plants and instead employed a more conducive model, the unicellular green algae Chlamydomonas reinhardtii. Here, a well-established genetic tool box allows the generation of knock-down/out lines and functional tagging of proteins of interest, while our analytical methods established for plants remain applicable. Chlamydomonas possess a haploid genome with less genetic redundancy than diploid plants. Each cell contains only one single plastid. Different from Arabidopsis, plastome transformation is relatively easy which will allow us to generate plastid expression / translation reporter lines and genetically plastome encoded ion/pH biosensors. The cell-cycle of Chlamydomonas cultures can be synchronized and chloroplast/cell division of individuals can be closely monitored by single cell live imaging. Photosynthetic performance of single algae cells will be probed by microscopy Pulse Amplitude Modulation (PAM). Elemental composition of genotypes will be analyzed by Total Reflection X-ray Fluorescence Spectroscopy (TXRF). In parallel, we aim on dissecting protein function by obtaining biochemical and structural information from in-vitro approaches. The homolog of KEA1/2 in Chlamydomonas will be the starting point for our study before focusing on the functional characterization of other plastid localized carriers.

We seek to train a highly motivated PhD student on this project. The ideal candidate would have basic experience in plant and/or algae molecular biology and a solid background in biochemistry and cell biology.

References:

DeTar RA, Barahimipour R, Manavski N, Schwenkert S, Höhner R, Bölter B, Inaba T, Meurer J, Zoschke R, Kunz HH. Loss of inner-envelope K+/H+ exchangers impairs plastid rRNA maturation and gene expression. Plant Cell. 2021 Aug 13;33(7):2479-2505. doi: 10.1093/plcell/koab123. Erratum in: Plant Cell. 2021 Sep 18;: PMID: 34235544; PMCID: PMC8364240.

Aranda-Sicilia MN, Aboukila A, Armbruster U, Cagnac O, Schumann T, Kunz HH, Jahns P, Rodríguez-Rosales MP, Sze H, Venema K. Envelope K+/H+ Antiporters AtKEA1 and AtKEA2 Function in Plastid Development. Plant Physiol. 2016 Sep;172(1):441-9. doi: 10.1104/pp.16.00995. Epub 2016 Jul 21. PMID: 27443603; PMCID: PMC5074627.

Schroda M, Remacle C. Molecular Advancements Establishing Chlamydomonas as a Host for Biotechnological Exploitation. Front Plant Sci. 2022 Jun 29;13:911483. doi: 10.3389/fpls.2022.911483. PMID: 35845675; PMCID: PMC9277225.

 


Dr. Macarena Marín (Genetics)
Title: Life within a cell

Description:
Nitrogen-fixing rhizobia can live endosymbiotically inside specialized cells in the roots of legume plants. No other living cell-type can host rhizobia. Despite the uniqueness of this process and its importance for agriculture, our molecular understanding of the cellular adaptations required to host rhizobia inside root nodule cells remains limited. By comparing the transcriptomes of root nodules that can and cannot host rhizobia, we identified candidate genes that are likely to mediate this process. Among these, genes with functions associated with cell wall plasticity and cell expansion were specifically upregulated in infected nodules. In this project, we will investigate the function of these genes and evaluate if they play a role in hosting endosymbiotic bacteria. To this end we will: i) generate mutants of selected candidates using CRISPR/Cas editing and assess their phenotypes, ii) analyze the spatiotemporal control of promoters driving the expression of candidate genes, and iii) use advanced microscopy and mathematical modelling to understand the relation between cell wall plasticity and cell expansion. The molecular understanding of how plant cells host endosymbiotic bacteria will aid in the long-term goal of transferring endosymbiotic nitrogen-fixation to other plants, which will hopefully reduce the need of using environmentally harmful nitrogen fertilizers.

Contact information:
If you are interested in this project, contact Macarena Marin

 

 Prof. Dr. Richard Merrill (Evolutionary Biology)                                                                                         Title: Genetics of visual preference behaviours in Heliconius butterflies

Heliconius butterflies are well known for their bright warning patterns that vary across populations. These warning patterns are used to warn predators that they don't taste very nice. However, they have a second function during mate choice, as males invariably prefer to court and mate with females that share their own colour pattern. This presents an important pre-mating reproductive barrier to gene flow, and has likely contributed to speciation in the butterflies. We have been studying the genetic basis of shift in visual preference behaviour in two sympatric species of Heliconius butterflies, the white H. cydno and the red H. melpomene, for many years and have now identified a handful of candidate genes expressed in the brain. This project would begin to functionally test these candidates with Crispr/Cas9 knockout experiments and associated behavioural experiments. This could be combined with further studies, including for example ATAQseq and antibody staining to further understand the mechanisms underlying this shift in behaviour. This is just one possible project on Heliconius butterflies available, and interested candidates are strongly encouraged to contact Prof. Richard Merrill

Relevant publications:

Rossi, M., Hausmann, A.E., Thurman, T., Montgomery, S.H., Papa, R., Jiggins, R.D., McMillan, O. & Merrill, R.M.(2020) Visual mate preference evolution during butterfly speciation is linked to neural processing genes. Nature Communications11: 4763.

Merrill R.M., Rastas P., Martin S.H., Melo, M.C., Barker S., Davey, J., McMillan W.O., Jiggins, C. (2019) Genetic dissection of assortative mating behavior. PLoS Biology 17: e2005902


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