The Marie Sklodowska-Curie Doctoral Network"ZooCELL: Tracing the evolution of sensory cell types in animal diversity: multidisciplinary training in 3D cellular reconstruction, multimodal data analysis and science outreach" is recruiting 12 Doctoral Candidates (DCs). The doctoral candidates will be hired in one of the following institutions:  the European Molecular Biology Laboratory (3), Stazione Zoologica Anton Dohrn Napoli (1), Friedrich Schiller University Jena (1), Institut de Génomique Fonctionnelle de Lyon (1), Institut de la Mer de Villefranche-sur-mer (1), Heidelberg University (1), Uppsala University (1), Museum fur Naturkunde Berlin (1), University College London (1) and University of Exeter (1)

Scientific background

All animals need to sense their environments. The ability to detect light, temperature, chemicals, sound, vibrations and other stimuli depends on an extraordinary range of sensory cell types. The diversity and relationships between these receptor cells across the animal phyla, how they have been adapted, reused, tweaked and sometimes lost, is little known but is crucial for understanding how animals survive and thrive in diverse environments. Most sensory cells are characterised by complex shapes and molecular machinery, first discovered by meticulous electron microscopy in the past decades. More recently, this has been complemented by genetic studies of their development and differentiation in various animal models. These two research programmes have, however, largely remained separate, and a unified morphological and molecular understanding of how the diversity of animal sensory cells has evolved is lacking. Our aim in ZooCELL is to create a comprehensive view of sensory cell type evolution based on the discovery of recurrent patterns of genetic and subcellular structure across a wide range of new animal models. To this end, we will combine single-cell genomics, correlative light and electron microscopy, Artificial Intelligence, and reverse genetics approaches in these species. ZooCELL will bring together Europe’s world-leading expertise in these disciplines, and thus contribute to building the field of comparative integrative cell biology in animals. While training the next generation of doctoral students in these novel interdisciplinary techniques, we will develop new tools for combined molecular and morphological comparative analyses of cell types. Our interdisciplinary, intersectoral and international training programme will also include dissemination and public outreach, and the comprehensive training provided will enable our graduate students to assume leadership roles in academia, industry and science outreach.

About the network 

The ZooCELL network brings together 8 beneficiaries and 7 associated partners, located in 6 different countries (France, Germany, Italy, Netherlands, Sweden and UK) and one intergovernmental organisation (EMBL-ZooCELL coordinator). 12 Doctoral candidates will enjoy a multi-disciplinary and international environment with plenty of training opportunities and exchange with all labs involved in the Network.

Details of the offered positions

• For detailed information on each position, including how to apply and the application deadline, please refer to each position description below. Please note that the application deadline varies for each position. 
• If you wish to apply to more than one position, please apply individually to each of them.

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DC1:  “Large-scale automated segmentation of cells, including tools for unbiased analysis of cellular morphology”

Host: European Molecular Biology Laboratory (EMBL), DE.

PhD Awarding institution: Heidelberg University (UHEI), DE.

Primary Supervisor: Dr. Anna Kreshuk.

Project duration: 36 months.

Project description: Morphological analysis of cells in tissues is contingent on our ability to perform cell segmentation in vEM image stacks. While an expert biologist can delineate cell membranes in vEM data manually, this approach does not scale beyond a few cells of interest, making automated cell segmentation algorithms a prerequisite for whole-organism and cross-organism analysis. State-of-the-art segmentation methods, such as the ones used in recent atlas-building efforts or large-scale connectomics studies, operate in the paradigm of supervised machine learning, training the neural networks on densely (manually) annotated reference sub-volumes of the data. The first objective of this project is to significantly relax the requirements to the amount and density of training data, enabling practical use of such methods for multiple datasets from different species acquired on different microscopes. The second objective is to establish a set of unbiased descriptors of the segmented cells, including both shape and ultrastructure features which will allow to group and explore morphologically similar cells across organisms. In addition to cellular-level descriptors, we will develop methods to characterise areas of tissue and enable the search for similar features across datasets. In more detail, we will approach automatic segmentation as both a transfer learning problem from the few available datasets, including the Platynereis dumerilii atlas, and a weakly supervised segmentation problem where manual labels for novel ultrastructural elements will be introduced in a targeted manner. Building on recent success stories for single-cell morphology analysis, our cell descriptors will be based on unsupervised machine learning, exploiting biological priors and targeted manual labels for validation and quality control.

Application deadline: 14th October 2024

How to apply: Candidates shall apply via the EMBL International PhD program at the following linkand express their interest in this position within the group of Anna Kreshuk.

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DC2: “The sea urchin larval anterior nervous system: sensing light and food availability to modulate growth and swimming behaviour”                                              

Host  institution: Stazione Zoologica Anton Dohrn (SZN), IT.

PhD Awarding institution: Friedrich Schiller University Jena (FSUJENA), DE. 

Primary Supervisor:  Dr. Maria I. Arnone.

Co- Supervisor: Prof. Dr. Andreas Hejnol.

Project duration: 36 months.

Project description: The sea urchin pluteus larva spends from few to many weeks in the water column, where it is exposed to a complex environment. Therefore, these larvae have evolved mechanisms to adapt to changing, e.g., temperature, light, food conditions. A well-described example is the phenotypic plasticity of larvae depending on food availability that produces plutei with longer arms when food is scarce. Building on the previous knowledge acquired in the Arnone lab, where a pair of photoreceptor cells producing the TRH neuropeptide (TRHergic-PCRs) placed at either side of the Apical Organ (AO) were found to mediate phenotypic plasticity, the project aims at: i) reconstructing the microanatomy and connectome of the Paracentrotus lividus 4 day larva AO using serial vEM;  ii) obtain a single cell transcriptomics atlas of the 4-day larva; iii) placing the transcriptionally identified AO sensory cells and adjacent TRHergic-PCRs onto the 3-D ultrastructural map using correlative microscopy approaches; iv) map the interconnection between the TRHergic-PCRs and the anterior nervous system; v) functionally perturb sensory signalling by pharmacology and/or gene loss of function.

Required applicant profile: Experience in developmental and/or evolutionary biology, electron microscopy, bioinformatics or neurobiology is advantageous.

Application deadline: 28th June 2024

How to apply: To apply to this position, visit the following link.

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DC3: “The origin and evolution of gravitational sense organs in acoelomorphs and

beyond”

Host and PhD Awarding institution: Friedrich Schiller University Jena (FSUJENA), DE.

Primary Supervisor: Prof. Dr. Andreas Hejnol.

Project duration: 36 months.

Project description: The research group, headed by Andreas Hejnol, studies the evolution of animal organ systems using a broad diversity of animal taxa (e.g. nemerteans, priapulids, rotifers, gastrotrichs, acoelomorphs). The group is particularly interested in studying the molecular and cellular basis of organ system development using a comparative approach. The project addresses the question about the evolution of gravitational sensory organs across multicellular animals. Different animal lineages use differently shaped organs and cell types for sensing gravitation. Some of these organs are very prominent (statocyst in Acoelomorpha, Cnidaria and ctenophores) in other lineages the gravitational sense, although present, is not yet discovered. The aim of this project is to use single-cell transcriptomics, in situ hybridization and ultrastructural methods to characterize in detail gravitational sense organs in different animal lineages. The candidate will conduct comparative developmental transcriptomic analyses, detect commonalities and differences in different gravitation-sensing organs in e.g. acoelomorphs, priapulids, brachiopods and hemichordates.

The embryology/development and differentiation of these tissues will be studied using techniques such as Histology, Transmission Electron Microscopy, molecular biology, live-imaging, and single-cell sequencing. The successful candidate will work in close association with the group leader and other lab members with the aim to eventually contribute to the further development of the project in line with his/her interests.

Required applicant profile:

•       Experience in molecular biology and embryology methods is essential while experience in morphology and bioinformatics is highly desirable.

•       A background in evolutionary biology is beneficial.

•       A high motivation and passion for science is essential. 

•       Ability to work both independently and in close collaboration with others in a structured manner.

*Position filled*

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DC4: "Neurosensory cell types in the hydrozoan planula larvae: seeking the transcriptional basis of morphological diversity"

Host  institution: Institut de la Mer de Villefranche (IMEV), FR

PhD Awarding institution: Sorbonne University (SU), FR 

Primary Supervisor:  Dr. Evelyn Houliston.

Co- Supervisor: Dr. Richard Copley.

Project duration: 36 months.

Project Description: Sensory cells around the aboral pole of the hydrozoan Clytia planula larva mediate responses to environmental cues, but their precise nature and function are unknown. DC4 will relate differences in gene transcription between Clytia planula sensory cell types to morphology, function and developmental history. S/he will characterise the structure and organisation of specific types of Clytia planula neural and neurosensory cell, defining their distinct morphological features by light microscopy techniques in combination with vEM (collaboration with other network fellows/EMBL). S/he will extend scRNA-seq datasets to find drivers and effectors of (i) mature cell type identity, (ii) morphology, and (iii) fate specification, determining the function of specific transcription factors identified by these comparisons, and of the corresponding cell types, using gene knockdown approaches. S/he will collaborate with the other network partners to compare cell type genotype/phenotype across species.

Required applicant profile:   Strong motivation for questioning biological mechanisms and concepts. Training in cell, molecular and developmental biology preferred. Bioinformatics skills would be an advantage

*Position filled*

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DC5: Mapping cell type diversity in the arthropod leg

Host  institution: Institut de Génomique Fonctionnelle de Lyon (IGFL)- CNRS, FR.

PhD Awarding institution: École Normale Supérieure de Lyon (ENSL), FR. 

Supervisors:  Dr. Michalis Averof and Dr. Mathilde Paris.

Project duration: 36 months.

Project description: Arthropod legs are multi-purpose organs, containing diverse cell types involved in sensing (e.g. sensory organ neurons, glia and accessory cells), locomotion (muscles, tendons, joints), protection and immunity (epidermis, blood cells), as well as numerous cell types with unknown functions. The recruited PhD student will generate a multimodal cell atlas, integrating the molecular profiles of more than 15 distinct cell types that make up the arthropod leg with ultrastructural data, and will identify the functions and evolutionary relationships of these diverse cells.

The student will accomplish this in the crustacean Parhyale hawaiensis, which we have already started to explore using scanning electron microscopy and single-cell transcriptomics. Parhyale legs contain more than 15 cell clusters discovered by single-nucleus RNAseq, corresponding to epidermal, neuronal, muscle and blood cells, as well as several yet unknown/uncharacterized cell types. The student will study the Parhyale leg at subcellular resolution using multi-beam SEM, to identify cell types based on ultrastructure, and will associate each of these with the corresponding transcriptional signatures using correlative light and electron microscopy approaches. Microanatomy and transcriptional profiles will provide a rich set of features for exploring the identities of these cells, their functions, and their relationships to the cells of other animals. Genetic tools such as transgene-mediated cell ablation or CRISPR-mediated gene knock-outs (already established in Parhyale) will be used to test the functions of selected cell types and the role of key regulators that define them.

Required applicant profile: Applicants should have a Masters degree in science, preferably in Biology. Practical experience in molecular, cell or developmental biology, microscopy and/or image analysis will be an advantage. Strongly motivated students from other disciplines should also apply. Applicants should be able to communicate fluently in English.

*Position filled*

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DC6: “Identification of conserved cellular functional modules in sensory neuron evolution”

Host: European Molecular Biology Laboratory (EMBL), DE

PhD Awarding institution: Heidelberg University (UHEI), DE.

Primary Supervisor: Prof. Dr. Detlev Arendt

Project duration: 36 months

Project description: Our aim to elucidate the evolution of the bilaterian brain requires an in-depth understanding of the sensory cell types that innervate the distinct ancient brain parts such as the mechanosensory girdle and the apical nervous system. We will study the evolution of sensory cell types, with a strong emphasis on head mechanosensory cells and chemo-/photosensory-secretory cells of the apical nervous system. We will focus on marine animal model systems that exhibit a differentiated nervous system at life cycle stages composed of relatively few cells so that whole-body cellular resolution can be obtained, as already shown for the annelid P. dumerilii and as also manifest for pre- and postmetamorphic stages of the chiton Acanthochitona crinita and juvenile nemerteans, which together represent a broad range of Lophotrochozoa phyla and will be studied here. For these animals, we will attempt to create whole-body cellular atlases for pre- and postmetamorphic juveniles in P. dumerlii and A. crinita, and for juvenile nemerteans, in collaboration with other ZooCELL doctoral candidates. This effort will combine gene expression and ultrastructural information for the entire body, as a prerequisite for the identification of coregulated gene sets correlating with co-occurring morphofeatures together with DC1 (EMBL). This way the project aims to find and define conserved cellular functional modules characteristic for mechanosensory and sensory-secretory cell types.

*Position filled*

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DC7: “Application of a high-throughput array tomography vEM pipeline to study the diversity of marine larvae and sensory cell types”

Host institution and PhD Awarding institution: Centre for Organismal Studies (COS) - Heidelberg University, DE.

Primary Supervisor:  Prof. Dr. Gaspar Jekely.

Project duration: 36 months.

Project description: The project will offer in-depth training in the volume electron microscopy (vEM) of marine larvae. One goal will be to obtain a high-quality full-body EM volume of a six-day-old Platynereis dumerilii juvenile and analyse the volume in collaboration with other students of the network. The successful candidate will also be instrumental in coordinating other vEM projects in the network. The project will also include extensive data analysis, including skeletonisation, working with volume-segmented data, cell-type and connectome annotation, and network analysis. The project will inform the evolution of larval form and sensory cell types.

Required applicant profile: Applicants should have a Masters degree in science, preferably in Biology. Practical experience in molecular, cell or developmental biology, microscopy and/or image analysis will be an advantage. Strongly motivated students from other disciplines (e.g. physics, biophysics) are also encouraged to apply. Applicants should be able to communicate fluently in English. German language skills are not required.

Application deadline: Provisional deadline is 30th October 2024, but we will be reviewing and processing applications as they are received.

How to apply: Please send the following documents as a single PDF to gaspar.jekely@cos.uni-heidelberg.de

• A motivation letter describing your research interests and why you apply for the position
• Your Curriculum Vitae
• MSc&BSc diploma incl. Grade Transcripts
• Contact details of two referees

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DC8: “Comparative structure and evolution of the ecdysozoan head”

Host  institution and PhD Awarding institution: Uppsala University (UU), SE

Primary Supervisor:  Dr. Graham Budd

Co- Supervisor: Dr. Ralf Janssen

Project duration: 36 months

Project description: The priapulid worms are a particularly interesting group as they are large and very poorly studied; furthermore, they bear a close resemblance to worms present in the Cambrian fossil record. In order to elucidate the origin of derived ecdysozoan anterior systems, DC8 will therefore study the detailed cellular morphology of the anterior of the priapulid worm Priapulus caudatus, using electron microscopy (array tomography SEM, TEM, DESEM). DC8 will also generate a single-cell transcriptomic dataset for Priapulus. The data on its cellular morphology thus obtained will then be compared to EM data on other ecdysozoans, notably the worm C. elegans, and the onychophoran Euperipatoides. In particular, the structure of the nervous system and any sensory structures, essentially unknown up to now, will be characterised and compared in a phylogenetic context. This project will be placed within an evolutionary framework informed by the excellent fossil record of ecdysozoan evolution in the Cambrian.

Required applicant profile: Applicants should have a Masters degree in science, preferably in Biology. Practical experience in microscopy and/or image analysis will be an advantage. Strongly motivated students from other disciplines (e.g. palaeobiology) are also encouraged to apply. Applicants should be able to communicate fluently in English.

*Position filled*

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DC9: “Orientation in lophophorates”

Host  institution: Museum für Naturkunde Berlin (MFN), DE

PhD Awarding institution: Humboldt-University Berlin (HUBER), DE

Primary Supervisor:  Prof. Dr. Carsten Lueter

Project duration: 36 months

Project description: The candidate will conduct an in-depth study of the morphology of the frontal nervous system and esp. apical organs based on serial electron microscopy (TEM, FESEM) to 3D-reconstruct (1) the shape of individual neuronal cells in apical organs and the surrounding nervous system inkl. receptor cells, (2) the interconnection between these and the frontal nervous system, and (3) the overall architecture of these sensory structures. Supported by scRNA-seq data partly gathered during the preceding project EvoCELL, immunohistochemistry and new AI-technologies the candidate will characterize developmental stages of the inarticulate brachiopod Novocrania anomala, to be collected at Bergen, Norway, and compare them to data on other lophophorate and lophotrochozoan groups investigated within work packages 1-4 of the ZooCELL network. The goal is to finally decipher interdependencies between nervous system morphology (plasticity) and developmental and environmental cues in these groups. Additionally, as the MfN coordinates the science outreach part of the project, the candidate will be involved in the setup and maintenance of the project’s homepage and activities related to science communication.

Required applicant profile: The candidate preferably has a background in evolutionary morphology of invertebrates and is familiar with high-resolution microscopy techniques, such as TEM, SEM, CLSM etc. Knowledge in molecular biology and a strong interest in science communication are advantageous. 

Application deadline: 30th November 2024

How to apply: To apply to this position, visit the following link. See "academic staff" section.

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DC10: “From transcriptome to morphome: development of a correlative toolbox to perform vEM on targeted cell types”

Host: European Molecular Biology Laboratory (EMBL), DE.

PhD Awarding institution: Heidelberg University (UHEI), DE.

Primary Supervisor: Dr.Yannick Schwab.

Project duration: 36 months.

Project description: The morphome quantitatively describes morphological diversity at multiple scales: At the subcellular level, the set of organelles, their arrangement and associations define functional units that are relevant to cell types (e.g. sarcomeres in muscles, secretory granules in gland cells). The correlation of expression profiles to ultrastructural phenotypes has so far been very difficult. In this project,  will focus on the development of tools to bridge scRNAseq to volume Electron Microscopy (vEM), with the specific goal to identify cell types by their expression profile and target these for detailed sub-cellular description by vEM and subsequent image analysis. Within the consortium, collaborations will lead to the investigation of a few model systems (D.Priapulus, Novocrania, and/or Acanthochitona), with a strong focus on the planula larva of the hydrozoan Clytia, in close collaboration with the group of Evelyn Houliston  (CNRS-IMEV). The PhD candidate will  i) develop correlative in-situ hybridisation and transmission EM workflow to identify cell types and to then ii) further their morphological characterisation by acquiring vEM datasets and iii) performing detailed image analyses (in collaboration the Kreshuk lab). Resulting in a detailed description of the subcellular landscape, iv) parallels will be sought with the corresponding single-cell transcriptomes.

*Position filled* 

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DC11: “Homology of diverse lophotrochozoan larval types and the characterisation of apical organs”

Host and PhD Awarding institution: University College London (UCL), UK

Primary Supervisor: Prof. Dr. Max Telford

Project duration: 36 months.

Project description: Many marine animal species have indirect development via a larval stage - this is particularly true of the phyla within the major clade of Lophotrochozoa. These larvae are, at least superficially, similar across phyla but their homology is uncertain. The student will compare a distinctive larval feature that is similar across lophotrochozoan larvae – the apical organ. The student will analyse individual component cells of apical organs of multiple animal phyla (with a focus on the flatworm Prostheceraeus crozieri and the phoronid Phoronis mueller) they will characterise gene expression, cellular phenotype and connections between these cells and with other cells (eye spots, ciliary bands etc.). Demonstration of complex similarities would support homology of this larval structure across phyla. Broader comparisons will be made possible by collaboration across the network. The student will also be able to participate in work to resolve the phylogeny of the Lophotrochozoa.

Required applicant profile:

•       Experience in molecular biology and embryology methods is essential

•       Electron microscopy and bioinformatics are advantageous

•       A background in evolutionary biology is beneficial.

•       A high motivation and passion for science is essential.

*Position filled* 

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DC12: “Evolution of sensory systems for polychaete larval behaviour and development”

Host and PhD Awarding institution: University of Exeter (UNIEXE)

Primary Supervisor: Dr. Elizabeth Williams

Project duration: 36 months.

Project description: This project will compare the head sensory systems (antennae, cirri, nuchal organ) of closely related nereid polychaete species Platynereis dumerilii and Platynereis massiliensis. Platynereis dumerilii has free-swimming larvae while Platynereis massiliensis shows direct development. Initial studies indicated that sensory structures in P. massiliensis are reduced, for example, they lack antennae. The PhD candidate will analyse an available synapse-resolution serial EM dataset of a Platynereis dumerilii larva and obtain and analyse an EM series of an equivalent stage Platynereis massiliensis larva in collaboration with Professor Gaspar Jekely’s group at the University of Heidelberg. All neurons projecting from sensory head appendages will be reconstructed in both species. Synaptic connectivity maps will be complemented by the comprehensive mapping of conserved proneuropeptides and neurotransmitters and their receptors by a combination of immunostaining and hybridization chain reaction (HCR). The PhD candidate will also generate an atlas of neuroendocrine and nervous system markers in P. massiliensis for comparison with existing data from P. dumerilii. The candidate will compare cellular phenotypes at nanometer resolution between the two species with benthic vs pelagic development and correlate this with neuroendocrine molecular maps. To dissect inter-specific functional differences, the candidate will use neuropeptide pharmacology in both species. By comparing nervous system morphology and signalling in closely related pelagic and direct developing polychaete larval types, this project will contribute to our understanding of the evolution of larval sensory systems for navigation in the sea.

Required applicant profile: Applicants should have a Masters or First Class Honours degree in science, preferably in Biology, or equivalent qualifications. Practical experience in molecular, cell or developmental biology, microscopy (electron microscopy, confocal microscopy), behavioural and/or image analysis will be an advantage, however training for specific techniques will also be provided on the project. Applicants should have a strong enthusiasm for larval biology, sensory systems, evolution, development and/or marine biology and be able to work both independently and as part of a team.

*Position filled*