Vacant ESR PhD projects

ESR 1.5 The interplay between senescence and stem cells in tissue regeneration - de Bruin

ESR project

1.5

Title of project

The interplay between senescence and stem cells in tissue regeneration

We offer

A 4-year PhD student position in the interdisciplinary area of regenerative medicine.Your project will focus on investigating through which mechanisms senescent cells induce pluripotency (I), how such a persistent lock of stemness can impair tissue regeneration (II) and how this may affect tumor therapy resistance (III).

We ask

You hold a Master’s degree in Biology, (Bio)medical Science, (Veterinary) Medicine or in a related area. You have affinity with molecular and cell biology, are willing to conduct in vitro and in vivo experiments and  to thrive in a multidisciplinary research environment. Experience with biological processes as senescence, aging, cancer, regeneration and in vivo work are of benefit.

Department

You will be employed at the UU (UU), hosted by the Department of Pathobiology, Faculty of Veterinary Medicine and the Center of Molecular Medicine of the University Medical Center Utrecht (UMCU). This project is jointly supervised by Alain de Bruin, UU and Peter de Keizer, UMCU.

Description

Tissue regeneration relies on faithful differentiation of stem cells. However during aging the regenerative capacity of tissues  is impaired and the inhibitory mechanism on tissue stem cells are largely unknown   When healthy cells are irreparably damaged, they can enter a state called senescence (White et al. Nat Commun 2015). Senescent cells continuously secrete a range of molecules that alter their local milieu, the Senescence Associated Secretory Phenotype (SASP). As such, senescent cells have been found to be directly causative for tissue aging and loss of homeostasis (Baar et al. Cell 2017). We have observed that senescent cells are often flanked by cells that are in a state of pluripotency. Moreover, we have found that SASP factors can trigger stemness in healthy and cancer cells. In cancer cells, this makes them more resistant to treatment. In healthy cells, we hypothesize that SASP factors prevent differentiation of tissue stem cells and thereby impair tissue rejuvenation (de Keizer Trend Mol Med 2017) Together, this calls for investigation on how senescent and stem cells interact and how mitigation of their negative interplay may improve tissue regeneration during aging and affect migration of therapy-resistant cancer.

Requirements

  • You hold a Master’s degree in Biology, (Bio)medical science, Medicine or in a related area.
  • You have affinity with Molecular Biology, Cell Biology
  • Experience with biological processes as senescence, aging, cancer, regeneration and in vivo work are of benefit.
  • You are a person with excellent communication skills, able to effectively communicate scientific ideas and foster collaborations. You have a well-developed capability for independent thinking and are able to work independently within a dynamic team and can communicate proficiently in written and spoken English.

Contact person & more information

Prof. Alain de Bruin, Professor in Pathobiology, Faculty of Veterinary Medicine, A.deBruin@uu.nl

Dr Peter de Keizer, Assistant professor “Senescence in Cancer and Aging, Center for Molecular Medicine P.L.J.deKeizer@umcutrecht.nl

RESCUE

This project is part of RESCUE, a multidisciplinary, intersectoral and interdisciplinary PhD training programme in Regenerative Medicine and Stem Cells organised by UMC Utrecht (coordinator) and Utrecht University. RESCUE is partly funded by the European Commission under Horizon 2020's Marie Skłodowska-Curie Actions COFUND scheme. There are specific requirements with regards to English language and mobility for candidates who would like to take part in this programme. More information

ESR 1.7 Stem-cell guided personalized therapy for people with cystic fibrosis - Beekman

ESR project

1.7

Title of Project

Stem-cell guided personalized therapy for people with cystic fibrosis

We offer

A 4-year PhD student position in the interdisciplinary area of stem cell biology and preclinical drug development. Your project will focus on developing new therapies for treatment of people with the rare genetic disease cystic fibrosis.

We ask

You hold a Master’s degree in biomedical sciences, pharmaceutical sciences, or in a related area. You have affinity with translational medicine and stem cell biology and thrive in a multidisciplinary research environment. Experience with cell and organoid culture and working with primary cells are of benefit.

Department

Pediatric Pulmonology, Wilhelmina Children’s hospital, University Medical Center Utrecht, Utrecht University, Location Regenerative Medicine Center Utrecht, Uppsalalaan 8, Utrecht, The Netherlands.

Description

Cystic fibrosis (CF) is the most frequent life-shortening monogenetic disease in western countries, caused by mutation of an ion channel that is critical for proper ion and fluid transport at epithelial surfaces. New treatments that can restore the basic ion channel defect are causing a paradigm shift in treatment of CF, yet these treatments are insufficiently effective for the majority of people with CF. We are pioneering the use of patient-derived stem cells to study the ion channel defects in CF, how such defects can be restored, and to identify patients that can benefit from treatments (e.g. https://www.nature.com/articles/nm0717-796). This will involve the culture of 2D and 3D intestinal and airway organoids that will be used for precision medicine and to identify mode of action of newly identified potential therapies. Our current research team comprises of both laboratory and clinical scientists, and provides a highly translational environment for your PhD study.

Requirements

  • You have a Master in Biomedical or pharmaceutical sciences.
  • You have affinity with Stem cells and/or translational medicine.
  • Experience with cell/organoid culture/microscopy are of benefit.

Contact person & more information

Jeffrey Beekman, PhD. Associate Professor, Pediatric Pulmonology

RESCUE

This project is part of RESCUE, a multidisciplinary, intersectoral and interdisciplinary PhD training programme in Regenerative Medicine and Stem Cells organised by UMC Utrecht (coordinator) and Utrecht University. RESCUE is partly funded by the European Commission under Horizon 2020's Marie Skłodowska-Curie Actions COFUND scheme. There are specific requirements with regards to English language and mobility for candidates who would like to take part in this programme. More information

ESR 2.10 Developing a fully synthetic extracellular matrix to control stem cell fate - Boons

ESR project

2.10

Title of project

Developing a fully synthetic extracellular matrix to control stem cell fate

We offer

A 4-year PhD student position in the interdisciplinary area of regenerative medicine. Your project will focus on the chemical and enzymatic synthesis of extracellular matrix components such as complex carbohydrates and peptides for the construction of an artificial three dimensional extracellular matrix that will be explored to direct stem cell differentiation or organoid formation.

We ask

You hold a Master’s degree in chemistry or in a related area. You have affinity with synthesis of biomolecules such as complex carbohydrates and peptides and thrive in a multidisciplinary research environment. Experience with bioconjugation and material sciences and cell biology is of benefit.

Department

You will be employed at the University Utrecht, Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, David de Wied building, Universiteitsweg 99, 3584 CG Utrecht.

Description

Current tissue-engineering approaches employ poorly defined exogenous three-dimensional extracellular matrices to engineer new natural tissues from isolated cells. It is anticipated that greater control over materials properties and tissue responses can be achieved with well-defined synthetic analogs. The goal of this project is to design and prepare hydrogels that recapitulate functional properties of the extracellular matrix. The new materials will be explored as temporary scaffolds to guide new tissue growth and organization. They will be composed of natural polymeric scaffolds such as HA and CS that through contemporary bio-orthogonal chemistries will be modified by synthetic cell adhesion peptides and heparan sulfate oligosaccharides that can a recruit and stabilize specific morphogens to guide stem cell differentiation and proliferation. 

Requirements

You have a Master in Chemistry or related area. You have affinity with biological chemistry, synthesis of biomolecules and macromolecular chemistry. Experience with bioconjugation and cell biology are of benefit.

Contact person & more information

Geert-Jan Boons, Professor of Chemical Biology, g.j.p.h.boons@uu.nl

RESCUE

This project is part of RESCUE, a multidisciplinary, intersectoral and interdisciplinary PhD training programme in Regenerative Medicine and Stem Cells organised by UMC Utrecht (coordinator) and Utrecht University. RESCUE is partly funded by the European Commission under Horizon 2020's Marie Skłodowska-Curie Actions COFUND scheme. There are specific requirements with regards to English language and mobility for candidates who would like to take part in this programme. More information

ESR 2.11 Epicardial contribution to cardiac remodeling and repair - van Rooij

ESR project

2.11

Title of project

Epicardial contribution to cardiac remodeling and repair

We offer

You hold a Master’s degree in biomedical sciences, pharmaceutical sciences, or in a related area. You have affinity with cardiology and molecular biology and are motivated to do good science in a stimulating research environment.

We ask

You hold a Master’s degree in biomedical sciences, biomedical engineering, biomaterials, veterinary science or in a related area. You have affinity with biology and engineering, and thrive in a multidisciplinary research environment. Experience with horses is a plus, but not a requirement.

Department

You will work at the Hubrecht Institute, which is affiliated with the University Medical Center Utrecht, in the same building as the Regenerative Medicine Center Utrecht, Uppsalalaan 8, Utrecht, The Netherlands.

Description

Cardiovascular disease remains one of the leading causes of death worldwide. A better understanding in the underlying causes of pathological remodeling that takes place during disease could help in the development of new treatments opportunities.  While the heart consists of several cell types, the epicardium, which forms the outer layer of the heart, plays a key role in activating remodeling processes important for disease and repair. Here we aim to investigate how the epicardium contributes to cardiac remodeling and repair processes and which triggers are required to promote tissue recovery. To this end we will use human iPSC-derived cultures and suitable mouse models as a model system. 

Requirements

  • You have a Master in Biomedical or pharmaceutical sciences.
  • You have affinity with Cardiology 
  • You have experience with molecular biology and cell culture
  • You are motivated to do good science.

Contact person & more information

Prof. Eva van Rooij, Professor Molecular Cardiology at the UMCU Division Hart and Lungs, e.vanrooij@hubrecht.eu

RESCUE

This project is part of RESCUE, a multidisciplinary, intersectoral and interdisciplinary PhD training programme in Regenerative Medicine and Stem Cells organised by UMC Utrecht (coordinator) and Utrecht University. RESCUE is partly funded by the European Commission under Horizon 2020's Marie Skłodowska-Curie Actions COFUND scheme. There are specific requirements with regards to English language and mobility for candidates who would like to take part in this programme. More information

 

ESR 3.3 Radiation free 3D imaging and early treatment of spinal disorders - Castelein

ESR project

3.3

Title of project

Radiation free 3D imaging and early treatment of spinal disorders

We offer

A 4-year PhD student position in the field of applied regenerative bone research, coordinated from the orthopedic department within the Division Surgical Specialties, in Utrecht. Your project will focus on 3D imaging with a new  ultrasound device.

We ask

You hold a Master’s degree in medicine, medical biology or in a related area. You have affinity with orthopedics and the surgical skills to perform large animal experiments.

Department

The Department of Orthopedics at the UMC Utrecht works on musculoskeletal regenerative medicine with a focus on biomaterials, bioprinting, bone biology, and engineering towards implementation in the clinical practice. The research of the group is conducted at the Regenerative Medicine Center Utrecht.

Description

Spinal disorders and related pain and morbidity has huge implications for the individual concerned and is one of the most prominent economic health burdens for society. Unfortunately, there is very little knowledge about the etiology and no risk factors have been identified for these pathologies. Furthermore, virtually nothing is known of the normal vs. the pathologic development of the spine during growth. There is a large body of evidence that a harmonious development of the spino-pelvic alignment is a prerequisite for good functioning and many of the disorders of later life are thought to be associated with life style and may arise at young age during spinal growth and development. Yet, it is unknown under which conditions a spine ideally develops into a healthy status or is prone to development of diseases such as e.g. scoliosis, (hyper)kyphosis or other mal-alignment. In addition, it is unknown what the subsequent growth stages are of a normal healthy developing spine. This knowledge will improve insight in etiology as well as better treatment regimens for these children

 

The objective of the current PhD project is

i) to assess the phases of development of the normal spine with a recently validated radiation-free imaging method using 3D ultrasound echography, and

 ii) to identify risk factors for the development of spinal disorders during childhood

iii) To explore the possibilities of the ultrasound imaging technique for real time (functional) measurements of the spine

iiii)) Apply the 3D and functional data to develop optimal surgical and bracing techniques

The PhD candidate will be part of a team of researchers with specific knowledge of orthopedic surgery, spinal disorders and medical imaging.

Requirements

  • You have a Master in medicine, medical biology or related science
  • You have affinity with research of the skeleton and medical imaging
  • You can travel and stay to collaborating research facilities overseas (Hongkong)
  • Experience with statistics and methodology are of benefit

Contact person & more information

Prof. R.M. Castelein, Orthopedic surgeon, r.m.castelein@umcutrecht.nl

Dr M. Kruyt Orthopedic surgeon, mkruyt@umcutrecht.nl

RESCUE

This project is part of RESCUE, a multidisciplinary, intersectoral and interdisciplinary PhD training programme in Regenerative Medicine and Stem Cells organised by UMC Utrecht (coordinator) and Utrecht University. RESCUE is partly funded by the European Commission under Horizon 2020's Marie Skłodowska-Curie Actions COFUND scheme. There are specific requirements with regards to English language and mobility for candidates who would like to take part in this programme. More information

ESR 3.11 Immunomodulatory coating development for orthopedic application - Kruijt

ESR project

3.11

Title of project

Immunomodulatory coating development for orthopedic application

We offer

A 4-year PhD student position in the field of applied regenerative bone research, coordinated from the Department of Orthopedics within the Division Surgical Specialties, in Utrecht. Your project will focus on the development of immunomodulatory coatings for orthopedic implants. You will be part of a team of researchers with specific knowledge of bone regeneration, biomaterials, and orthopedic surgery.

We ask

You hold a Master’s degree in biomedical science, biomedical engineering, or in a related area. You have affinity with musculoskeletal regenerative medicine and are capable of bridging the gap between biology and biomaterials science. You are willing to perform animal experiments.

Department

The Department of Orthopedics at the UMC Utrecht works on musculoskeletal regenerative medicine with a focus on biomaterials, bioprinting, bone biology, and engineering towards implementation in the clinical practice. The research of the group is conducted at the Regenerative Medicine Center Utrecht.

Description

Different biomaterials are used for the reconstruction of bone and joints in orthopedic and trauma surgery. A balanced inflammatory response is thought to potentiate bone formation through the regulation of pro-osteogenic and -angiogenic cytokines/growth factors at the biomaterial interface. The aim is to develop implant coatings that boost physiological bone healing by targeting immune cells.
First, you will identify immune modulatory compounds that promote osteoblast differentiation in vitro. For this purpose, you will used cell culture and/or small animal models that allow you to study the close interaction between stromal cells and different immune cell subsets. Subsequently, you will incorporate promising compounds in a coating formulation for biodegradable ceramics and metal implants. The coating formulation should be designed to control the release profile, and maximize its immunogenic and bone-inductive properties.

Additional strategies such as compound encapsulation or co-delivery methods could be explored to better target the appropriate cell type. Moreover, bioprinting or additive manufacturing techniques can be applied to develop implants with specific design for use in complex fractures or the spinal column. Promising strategies are tested for effectiveness in animal models.

Requirements

  • You have a Master in biomedical science, biomedical engineering, or in a related area.
  • You have affinity with musculoskeletal regenerative medicine and strong knowledge of biology
  • You have experience with cell culturing
  • You are willing to perform animal experiments
  • Previous experience in immunology, engineering and/or biomaterials research is a great benefit
  • You are willing to temporarily work at collaborating research facilities in the Netherlands and overseas

Contact person & more information

Dr M.C. Kruijt, Kruyt@umcutrecht.nl

Dr J. Alblas, J.alblas@umcutrecht.nl

UMC Utrecht, Division Surgical Specialties, Department Orthopaedics.

RESCUE

This project is part of RESCUE, a multidisciplinary, intersectoral and interdisciplinary PhD training programme in Regenerative Medicine and Stem Cells organised by UMC Utrecht (coordinator) and Utrecht University. RESCUE is partly funded by the European Commission under Horizon 2020's Marie Skłodowska-Curie Actions COFUND scheme. There are specific requirements with regards to English language and mobility for candidates who would like to take part in this programme. More information