Tardigrades are extremophile organisms, capable of surviving in the harshest environments. In recent years, their survivability has been linked to the presence of specific proteins, while lipids have largely been overlooked. In this project, you will focus on characterizing tardigrade lipidomes throughout each life stage and their adaptations to extreme situations. Therefore, you will apply a broad array of fundamental biochemical and biological methods, which range from lipid biochemistry to fluorescence imaging.
We are seeking a highly motivated student with a bachelorâs degree in biochemistry or a related field and a strong interest and drive. While hands-on experience in lipid biochemistry and molecular biology is desirable, it is not essential. We offer a highly interdisciplinary environment at the interface of cell biology and biochemistry.
If you are interested in pursuing your master’s thesis with us, please submit a motivation letter, CV, and transcript of records to Pavel Barahtjan ([email protected]), with the subject line âMSc thesis â Applicationâ. The duration of the thesis will comply with the regulations of the studentâs university (preferably a minimum of 6 months) and can begin immediately. The working language is English.
Neurons are highly polarized cells with distinct structural and functional domains: the cell body (soma), and neurites (axons and dendrites). These major domains differ radically in their morphology, signaling properties, cytoskeletal organization, and physiological functions. The differences are vital to the functional diversity that give neurons a unique role in the human body. A great deal of focus has been placed on the understanding and localization of molecules such as RNAs and proteins. But very little is known about the role of lipids, which play central roles in the biology of neurons, and whose alteration has been linked to a wide range of diseases 1. Distinguishing the lipid content of soma and neurites might yield important insights because of mounting evidence that local protein and lipid synthesis play crucial roles in neurite functions2. To achieve this, human iPSC-derived neurons are cultured in microporous membranes that permit a separation of soma from the neurites for the lipid profile. Interestingly, preliminary results have shown that specific sphingolipids are differently abundant between soma and neurites. This project will broaden our understanding of the compartmentalization and functions of neuronal lipids by applying new tools with the following aims:
1. to spatially profile the lipid composition of neuronal soma and neurites
2. study the functions of lipids at subcellular resolution
The student will gain experience with stem cells culture, mass spectrometry (MALDI imaging3 and LC-MS, chemical biology (click chemistry) and classical molecular and biochemical biology (qPCR, western blot and CRISPR-cas9) techniques to tackle these questions.
References:
1. Asaro, A. et al. Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling. Alzheimers Dement. 16, 1248â1258 (2020).
2. Zappulo, A. et al. RNA localization is a key determinant of neurite-enriched proteome. Nat. Commun. 8, 583 (2017).
3. Capolupo, L. et al. Sphingolipids control dermal fibroblast heterogeneity. Science 376, eabh1623 (2022).
Project duration: minimum 6 months
Interested students are welcome to contact: [email protected] and [email protected]
Cell fate transitions coupled to specific functions are essential for building multicellular organisms. From the earliest stages of embryogenesis through development and into ageing, proper fate acquisition drives the organization and function of complex tissues and organs. Not surprisingly, loss of cell fate at any stageâfrom embryonic specification to the lifelong maintenance of somatic and germline lineagesâis linked to a broad spectrum of diseases, including neurodegenerative disorders, metabolic syndromes, and reproductive failure. Despite its fundamental importance, the molecular mechanisms that govern fate determination remain incompletely understood.
The role of lipids in regulating cell fate has only recently emerged. Long regarded as secondary to external cues (e.g., cytokines and hormones) and cell-intrinsic mechanisms (e.g., gene expression, epigenetic state and cell cycle) that stabilize lineage identity, lipid signaling is now recognized as a pivotal regulatory layer in fate decisions. Nevertheless, how specific lipids shape fate specification remains poorly understood, leaving a major gap in our knowledge of lipid biology in cell fate regulation and its impact on health and disease.
This project will define how lipids regulate cell fate across the developmental continuumâfrom embryogenesis through tissue differentiation and maintenance in the mature organismâusing C. elegans and mice as model organisms.
The student will address two main aims:
- Spatially profile lipid composition across developmental stages and tissues to identify lineage-specific lipid signatures.
- Elucidate the functional roles of key lipid species in lineage specification and morphogenesis, with relevance to health and disease.
To achieve these aims, the student will perform high-resolution mass spectrometry imaging (MALDI-MSI) and targeted lipidomics (LC-MS) combined with lipidomic data analysis to map lipid distributions in situ. Molecular cloning and genome editing will be used to generate reporter lines and perturb lipid pathways. Functional consequences will be assessed through in vivo phenotyping, including developmental and behavioral assays, and immunofluorescence microscopy to visualize lineage markers. Additional techniques will include chemical biology approaches, as well as classical molecular and biochemical methods (qPCR, western blot), enabling a comprehensive link between lipid spatial organization, molecular function, and cell fate decisions across organismal development.
Duration: The thesis will follow the requirements of the studentâs home university, with a preferred minimum length of 6 months and the option to begin immediately.
Financial support: Guidance will be provided to students applying for fellowships to cover expenses during the thesis.
Contact: Interested candidates may reach out to Dr. Ilias Gkikas ([email protected]) and Prof. Giovanni DâAngelo ([email protected]) for further information.
Interested students are welcome to contact: [email protected] and [email protected]
Master Project
PIs : Giovanni DâAngelo (UPDANGELOâs lab) and Matteo Dal Peraro (LBM lab)
Starting date: as soon as possible
Background
The ceramide transfer protein (CERT, encoded by CERT1) mediates non-vesicular transfer of ceramide from the endoplasmic reticulum to the Golgi, a crucial step in sphingolipid metabolism. Mutations in CERT1 have been linked to a rare neurodevelopmental disorder, known as CerTra, which is caused by hyperactive forms of CERT that disrupt lipid homeostasis and lead to excess sphingomyelin production. Targeting CERT with small-molecule inhibitors offers a promising therapeutic strategy with both pharmacological and medical relevance.
Aim
This Masterâs project aims to conduct an in silico screen of a large compound library (over 100,000 molecules) to identify inhibitors of CERT. The focus will be on docking compounds to different functional domains of CERT, such as the START domain (which binds ceramide), the PH domain (which interacts with Golgi lipids), and regulatory regions. Special attention will also be given to how disease-associated mutations may alter binding sites and influence druggability.
Methods
The project will employ state-of-the-art molecular docking approaches in combination with modern AI and machine learning methods for compound scoring, clustering, and ADMET prediction. This will allow prioritization of structurally diverse compounds with favorable pharmacological properties. Computational modeling of mutant CERT proteins will also be performed to assess potential differences in compound binding compared to the wild-type protein.
Expected Outcomes
The study will generate a prioritized list of candidate inhibitors with high predicted binding affinity and promising drug-like properties. These compounds will form the basis for subsequent experimental validation in cellular assays and, eventually, in animal models of CerTra. Beyond identifying potential therapeutic leads, the project will also provide new insights into CERT structure-function relationships and the molecular basis of disease-causing mutations.
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For more information:
https://www.epfl.ch/labs/dangelo-lab/
https://www.epfl.ch/labs/lbm/
Please send us a CV and motivation letter to [email protected]