|Apply no later than||31 January 2021|
Metabolic syndrome (MetS) is a collection of pathological conditions that include abdominal obesity, increased blood pressure, insulin resistance and increased blood glucose and lipids. MetS is a risk factor for type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). Combined, these cardio-metabolic diseases form a heavy burden on our society and health care system. Clearly, increasing our knowledge on the molecular mechanisms contributing to the maintenance of metabolic homeostasis will provide tools to improve prognosis, diagnosis and ultimately treatment of patients with cardio-metabolic diseases.
EndoConnect partners have recently demonstrated that endo-lysosomal processes crucially control metabolic pathways in various tissues (e.g. liver and adipose tissue). Reciprocally, it has also been shown that metabolic changes can in turn shape the dynamics of the endo-lysosomal network, implying that endo-lysosomal processes and metabolism are strongly interconnected to maintain metabolic homeostasis. Despite the recent technological advances, there are still major gaps in our basic knowledge about how these vital processes are molecularly connected, and importantly, how this knowledge can be translated into clinical-grade products and can improve healthcare.
It is the ambition of EndoConnect to fill these knowledge gaps by training talented PhD students on how to use both cellular and in vivo models to study endo-lysosomal processes and metabolism at different levels, to provide them with an interdisciplinary and intersectoral training programme to use, implement and develop state-of-the-art technologies to connect basic molecular and cell biology research with metabolism, physiology and biomedical research. EndoConnect will accomplish this by bringing different research disciplines together to investigate the interrelationship between endo-lysosomal processes and (patho)physiology, with the focus on the role of endo-lysosomal processes in metabolism and cardio-metabolic diseases, such as Type 2 Diabetes, NAFLD and Cardiovascular Disease.
Are you interested? Please, check the different PhD positions available in the EndoConnect project! For a more detailed description of the PhD positions please visit the website: https://endoconnect.eu
Work package 2 - Molecular regulation of endo-lysosomal processes and cargo identification
On entering the endo-lysosomal network newly endocytosed integral membrane proteins and their associated proteins and lipids (together termed ‘cargos’), are subjected to one of two fate decisions: either they are sorted into the lysosome for degradation or they are retrieved from this fate and promoted for recycling back to the cell surface, the biosynthetic pathway or other specific organelles. A number of ancient and highly conserved protein assemblies serve to orchestrate these fate decisions (e.g. retromer, retriever, ESCPE-1), but their molecular regulation remain unclear. The aim is to establish the molecular details that define the relationship between degradative versus recycling fate decisions of internalized cell surface transporters and identify the proteins and cargos that play essential roles in nutrient uptake and metabolism.
PhD student 1 - Biochemical analysis of the assembly of multi-protein endosomal cargo sorting complexes
Host organisation: University of Bristol, UK (contact: Pete Cullen, )
PhD student 2 - Functional analysis of retriever and the CCC complex in endosomal cargo sorting in hepatocytes
Host organisation: University of Bristol, UK (contact: Pete Cullen, )
PhD student 3 - Understanding the fate of cargo via ubiquitination by E3 ligases and its role in hepatic function
Host organisation: AstraZeneca, Cambridge, UK (contact: Helen Boyd, ; Kevin Moreau, ). You are employed and the research is done at AstraZeneca. In addition, you are registered at the University of Amsterdam (AMC), the Netherlands where you will do the thesis defence.
Work package 3 - Spatial and temporal regulation of endo-lysosomal processes in lipid metabolism
Low-density lipoprotein (LDL) cholesterol is taken up by the cell through the LDL receptor (LDLR), a process highly dependent on the endo-lysosomal system. Endocytosed cholesterol is further transported to other cellular compartments. Changes in intracellular cholesterol concentrations modulate endo-lysosomal processes at a spatial and temporal level to maintain cholesterol homeostasis. Defects in these processes are correlated with impaired cholesterol uptake and intracellular transport, which can lead to hypercholesterolemia, cholesterol storage diseases and NAFLD. This work package will investigate the protein networks controlling endosomal cholesterol transport and lipid metabolism and their spatio-temporal regulation in living cells.
PhD student 4 - Uncovering the spatio-temporal regulation of endo-lysosomal lipid trafficking in control of metabolism
Host organisation: University Medical Centre Utrecht, NL (contact: Judith Klumperman, )
PhD student 5 - Coordination of endo-lysosomal cargo transport by NPC1 and post-NPC1 regulators of lipid metabolism
Host organisation: University of Helsinki, FI (contact: Elina Ikonen, )
PhD student 6 - Genome-wide functional genetic approaches to identify novel regulators of the endo-lysosomal network in control of lipid metabolism
Host organisation: Amsterdam Medical Centre, NL (contact: Noam Zelcer, )
Work package 4 - Regulation of endo-lysosomal processes by metabolic challenges
Metabolic mouse models of diet-induced obesity have indicated a regulatory role for glucose and lipid metabolism on the dynamics of endo-lysosomal processes at a transcriptional and post-transcriptional level. This work package will identify which endo-lysosomal processes are shaped by metabolic changes (fasting/feeding), aging, disease conditions of the metabolic syndrome, including NAFLD/NASH and cholesterol storage disorders.
PhD student 7 - The importance of the fasting-feeding transition for endosomal transport in the liver
Host organisation: Helmholtz Center Munich, DE (contact: Anja Zeigerer, )
PhD student 8 - High-throughput screening of endosomes in different metabolic/genetic backgrounds
Host organisation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, ES (contact: Albert Pol, )
PhD student 9 - Transcriptional regulation and functional validation of endo-lysosomal genes in metabolic diseases
Host organisation: Nebion, Zurich, CH (contact: Philip Zimmermann, ). You are employed and the research is done at Nebion. In addition, you are registered at the Helmholtz Institute, Munich, Germany, where you will do the thesis defence.
PhD student 10 - Identifying the molecular pathology and the role of endo-lysosomal components in fatty livers progressing to cancer
Host organisation: Utrecht University, NL (contact: Alain de Bruin, )
Work package 5 - The endo-lysosomal processes in metabolic disease development and therapeutic efficacy
Several lines of evidence highlight the importance of the endo-lysosomal system in the regulation of glucose and lipid metabolism but how they contribute to these pathways remain unclear. In addition, many therapies (such as Antisense oligonucleotides (ASOs) to treat hypercholesterolemia) are dependent on the endo-lysosomal system to enter the cell, how the endo-lysosomal system is involved in therapeutic potency is unclear. In this work package we will investigate how components of endo-lysosomal processes in different tissues contribute to the regulation of glucose and lipid metabolism and therapeutic efficacy.
PhD student 11 - The contribution of the endosomal sorting machinery to metabolism
Host organisation: University Medical Centre Groningen, NL (contact: Bart van de Sluis, )
PhD student 12 - Relevance of endosomal trafficking pathways for human lipid metabolism
Host organisation: University Medical Centre Groningen, NL (contact: J.A. Kuivenhoven, )
PhD student 13 - Role of endothelial lipoprotein transport for adipose tissue integrity and dyslipidemia
Host organisation: University Medical Centre Hamburg-Eppendorf, DE (contact: Jörg Heeren, )
PhD student 14 - The role of endo-lysosomal membrane proteins for energy metabolism in white and brown adipose tissues
Host organisation: University Medical Centre Hamburg-Eppendorf, DE (contact: Jörg Heeren, ; Pablo Sáez, )
PhD student 15 - Evaluating the endosomal transport and efficacy of therapeutics for metabolic liver diseases progressing to cancer
Host organisation: InteRNA technologies, Utrecht, NL (contact: Roel Schaapveld, ). You are employed and the research is done at InteRNA. In addition, you are registered at the Utrecht University, NL, where you will do the thesis defence.
As a PhD student in EndoConnect you will be part of an international team of young researchers. You will have your individual research project at one of the 12 host organisations located in the United Kingdom, Netherlands, Germany, Switzerland, Spain or Finland, focusing on your discipline of interest. To broaden your specialized training, you will undertake internships at complementary EndoConnect partner organization. In addition, you will follow advanced interdisciplinary courses by leaders in the field of molecular and cell biology, metabolism, physiology and biomedical research. Thus, you will be trained to become one of the future leaders in this emerging interdisciplinary field.
What do we need
- A(n) (almost) completed master’s degree in a discipline relevant to the PhD position(s) for which you apply.
- Strong motivation for scientific research in an interdisciplinary and international environment.
- Excellent English presentation and writing skills.
- Good organizational and communication skills, being a team-player.
Successful candidates must fulfil the criteria defined by the European Commission:
- As an Early Stage Researcher, you have to be in the first four years of your research career and have not been awarded a doctoral degree at the time of recruitment.
- At the time of recruitment by the host organisation, researchers must not have resided or carried out their main activity (work, studies, etc.) in the country of their host organisation for more than 12 months in the 3 years immediately prior to the reference date.
What do we offer
The PhD student will be appointed at and conform the conditions of the host organisation indicated for each position.
For more information about a specific position please contact the person indicated for that position.
You are invited to apply if you are interested in one or more of the PhD positions. Please indicate in your motivation letter for which PhD position(s) you are applying.
Applying for a job
Please use the the digital application form at the bottom of this page - only these will be processed. You can apply until 31 January 2021. Within half an hour after sending the digital application form you will receive an email- confirmation with further information.