Postdoc Tracing Weibel-Palade Bodies in Disease using Multi-beam Volume Electron Microscopy

Job description

In multi-beam electron microscopy (EM), a sample is scanned by tens of beams instead of the single beam in a traditional electron microscope. The increased throughput of multi-beam EM enables large-scale and volume microscopy and identification of rare events or different stages in a dynamic process. In this PostDoc project, our aim is to visualize the life-cycle of Weibel-Palade Bodies (WPBs) in the context of disease using multi-beam EM (FAST-EM) with correlative fluorescence light microscopy of patient-derived endothelial cells.

WPBs are ~1-5 µm-long rod-shaped secretory organelles that store the hemostatic protein Von Willebrand factor (VWF). Following vascular injury endothelial cells (ECs) immediately release large quantities of VWF into the circulation. Low circulating levels of VWF increase the risk of bleeding, such as in Von Willebrand disease, while elevated levels of VWF are associated with elevated risk of thrombosis. The composition and 3D architecture of WPB during fusion and secretion of VWF have thus far remained unclear. This is mainly because traditional electron microscopy approaches have been unable to reliably capture rare events and perform 3D analysis. As a Postdoc operating in a unique collaboration between TU Delft and Erasmus Medical Center, you will tackle this issue with the high-throughput multibeam FAST-EM developed at TU Delft.

You will work at both the Bierings group at Erasmus MC and the Hoogenboom group at TU Delft. You will start by implement our existing and published FAST-EM array tomography workflow for high-volume high-resolution mapping of WPBs in cultured endothelial cells.

Initial setup with endothelial cells (ECFCs) from healthy donors. When successful this will be extended to ECFCs derived from patients, e.g. with VWF trafficking defects (VWD, Storage pool disease, etc) and to ECs in which specific proteins of interest are depleted via shRNA or CRISPR targeting. You will then capture WPB trafficking events using fluorescence-guided high resolution EM imaging. WPBs and endolysosomal organelles will be labeled using fluorescent reporters or fluorophore-labeled antibodies. Finally, after succesful EM, you will work on segmentation, annotation and analysis of organelles in endothelial cells. We will train a convolutional neural network (based on U-net, e.g. similar to MitoNet that we used before on FAST-EM data) to automatically segment organelles from FAST-EM imaging data, with a focus on WPBs, endolysosomal compartments and vesicles of the ER-Golgi pathway. While you are expected to be actively involved in all aspects of the researc, expertise and support for all steps of sample preparation, EM acquisition and data reconstruction, and segmentation is available in both groups via technicians and PhD student on related projects.

Job requirements
You are a highly motivated and talented researcher with a strong interest in electron microscopy for life sciences and the development and application of novel methodology. You enjoy working in a multi-disciplinary environment at the interface of bio-medical research and instrument development and innovation, implementing new techniques to achieve tangible results. Embracing the opportunity to work with leading industrial partners, you know how to collaborate and achieve meaningful results geared to the development of pragmatic applications. You also put your curiosity to good use: you don’t take anomalies for granted and take the initiative to dig deeper and spar with experts. Harnessing your communication skills, you convince colleagues at TU Delft and Delmic of your approach, models and programs. And you enjoy interacting with and coaching talented bachelor and master students, while expanding your own knowledge and competencies.

You also have:

• PhD degree in Molecular Biology, (Applied) Physics, or a closely related field.
• Demonstrable skills in electron microscopy for life sciences, such as cellular EM, volume EM, or cryo-EM.
• A solid understanding and proven expertise in Python and the use of computational techniques, preferably neural networks, for data analysis and segmentation.
• Excellent communiction skills, connecting easily with people of diverse scientific backgrounds and being able to bridge research groups at two different locations.
• A proactive and curious mindset, with the ability to explore complex problems independently and collaboratively.
• A good command of spoken and written English, as you’ll be working in an internationally diverse community. You will also write scientific articles and your dissertation in English and participate in English-taught courses.
• An enthusiasm for coaching bachelor, master, and PhD students, and for presenting your work in scientific articles and international conferences.

TU Delft (Delft University of Technology)
Delft University of Technology is built on strong foundations. As creators of the world-famous Dutch waterworks and pioneers in biotech, TU Delft is a top international university combining science, engineering and design. It delivers world class results in education, research and innovation to address challenges in the areas of energy, climate, mobility, health and digital society. For generations, our engineers have proven to be entrepreneurial problem-solvers, both in business and in a social context.

At TU Delft we embrace diversity as one of our core values and we actively engage to be a university where you feel at home and can flourish. We value different perspectives and qualities. We believe this makes our work more innovative, the TU Delft community more vibrant and the world more just. Together, we imagine, invent and create solutions using technology to have a positive impact on a global scale. That is why we invite you to apply. Your application will receive fair consideration.

Challenge. Change. Impact!

Faculty Applied Sciences
With more than 1,100 employees, including 150 pioneering principal investigators, as well as a population of about 3,600 passionate students, the Faculty of Applied Sciences is an inspiring scientific ecosystem. Focusing on key enabling technologies, such as quantum- and nanotechnology, photonics, biotechnology, synthetic biology and materials for energy storage and conversion, our faculty aims to provide solutions to important problems of the 21st century. To that end, we educate innovative students in broad Bachelor's and specialist Master's programmes with a strong research component. Our scientists conduct ground-breaking fundamental and applied research in the fields of Life and Health Science & Technology, Nanoscience, Chemical Engineering, Radiation Science & Technology, and Engineering Physics. We are also training the next generation of high school teachers.

Click here to go to the website of the Faculty of Applied Sciences.

PhD Position Zeolites for PFAS Removal from Concentrated Waste Streams

Job description

Poly- and Perfluoralkyl substances (PFAS) are man-made persistent chemical compounds and have a negative effect on the environment and public health, due to their toxicity at very low concentrations. To remove low concentrations of organic micropollutants (OMPs) such as PFAS from water, nano- or reverse osmosis membrane technologies are increasingly considered and/or implemented by drinking water treatment plants. While such membranes produce safe drinking water, they also produce substantial volumes of highly concentrated waste streams (>5-fold higher PFAS concentrates than the treated water) that cannot be discharged directly without treatment. High-silica zeolites can selectively remove PFAS and other OMPs from such complex concentrates, and are potentially more effective than conventional activated carbon for PFAS removal when applied to concentrated waste streams. Previous research at TU Delft and elsewhere has already shown fast kinetics and high capacity for OMPs on zeolites in water with competing ions and organic compounds. The next-generation adsorbents we aim to develop should have (i) a higher affinity for OMPs, including short-chain PFAS, and (ii) a lower affinity for salts and organic matter, to minimize competition with OMP removal. In addition, to maximize re-use and longevity these adsorbents should also allow for (iii) frequent and (iv) effective regeneration.

This PhD is embedded in the recently funded NWO Perspektief project BlueVantage, connecting a diverse group of academics and societal stakeholders to inform safe and circular water (re)use across the water sector. You will be supervised by adsorption researchers from TU Delft and Wageningen University & Research (WUR). Our academic partners and our industrial project partner will produce tailored high-silica zeolites for your research.

You will take on the challenge to explore the selectivity of next-generation adsorbents for PFAS and adsorbent regeneration. You will:

• Drive and inform the design and selection of high-silica zeolites based on literature.
• Design experiments to test adsorbent materials with the goal of understanding performance and adsorption mechanisms for the target pollutants.
• Explore laboratory data using statistics and adsorption models to understand underlying trends, explore adsorption mechanisms and predict performance.
• Investigate loading and regeneration in lab experiments and potential pilot installations.
• Hold close feedback loops with industrial and academic partners.

The position is offered by Dr. Kim Lompe and promoter Prof. Dr. Luuk Rietveld at TU Delft and Dr. Gabriel Sigmund at WUR. All three will provide their specific expertise in adsorption and water treatment.

Job requirements
Need-to-have:

• A Master's degree in Water Treatment, Environmental Engineering or related field.
• Laboratory skills for basic water analysis.
• Data analysis skills for statistical analysis and data visualization and willingness to improve these.
• Initiative and engineering spirit to solve problems hands-on.
• Good communication skills to communicate with supervisor and colleagues.
• English Proficiency Test IELTS of 7.0 (scores of at least 6.5 in all sections) or TOEFL of 100 (scores of at least 21 for all sections). For more details please check the Graduate Schools Admission Requirements.

Nice-to-have:

• Experience working with adsorption materials.
• Programming skills (e.g. Python or R).

TU Delft
Delft University of Technology is built on strong foundations. As creators of the world-famous Dutch waterworks and pioneers in biotech, TU Delft is a top international university combining science, engineering and design. It delivers world class results in education, research and innovation to address challenges in the areas of energy, climate, mobility, health and digital society. For generations, our engineers have proven to be entrepreneurial problem-solvers, both in business and in a social context.

At TU Delft we embrace diversity as one of our core values and we actively engage to be a university where you feel at home and can flourish. We value different perspectives and qualities. We believe this makes our work more innovative, the TU Delft community more vibrant and the world more just. Together, we imagine, invent and create solutions using technology to have a positive impact on a global scale. That is why we invite you to apply. Your application will receive fair consideration.

Challenge. Change. Impact!

The Faculty of Civil Engineering & Geosciences
The Faculty of Civil Engineering & Geosciences (CEG) is committed to outstanding international research and education in the field of civil engineering, applied earth sciences, traffic and transport, water technology, and delta technology. Our research feeds into our educational programmes and covers societal challenges such as climate change, energy transition, resource availability, urbanisation and clean water. Our research projects are conducted in close cooperation with a wide range of research institutions. CEG is convinced of the importance of open science and supports its scientists in integrating open science in their research practice. The Faculty of CEG comprises 28 research groups in the following seven departments: Materials Mechanics Management & Design, Engineering Structures, Geoscience and Engineering, Geoscience and Remote Sensing, Transport & Planning, Hydraulic Engineering and Water Management.

Click here to go to the website of the Faculty of Civil Engineering & Geosciences.

Postdoc Tracing Weibel-Palade Bodies in Disease using Multi-beam Volume Electron Microscopy

Job description

In multi-beam electron microscopy (EM), a sample is scanned by tens of beams instead of the single beam in a traditional electron microscope. The increased throughput of multi-beam EM enables large-scale and volume microscopy and identification of rare events or different stages in a dynamic process. In this PostDoc project, our aim is to visualize the life-cycle of Weibel-Palade Bodies (WPBs) in the context of disease using multi-beam EM (FAST-EM) with correlative fluorescence light microscopy of patient-derived endothelial cells.

WPBs are ~1-5 µm-long rod-shaped secretory organelles that store the hemostatic protein Von Willebrand factor (VWF). Following vascular injury endothelial cells (ECs) immediately release large quantities of VWF into the circulation. Low circulating levels of VWF increase the risk of bleeding, such as in Von Willebrand disease, while elevated levels of VWF are associated with elevated risk of thrombosis. The composition and 3D architecture of WPB during fusion and secretion of VWF have thus far remained unclear. This is mainly because traditional electron microscopy approaches have been unable to reliably capture rare events and perform 3D analysis. As a Postdoc operating in a unique collaboration between TU Delft and Erasmus Medical Center, you will tackle this issue with the high-throughput multibeam FAST-EM developed at TU Delft.

You will work at both the Bierings group at Erasmus MC and the Hoogenboom group at TU Delft. You will start by implement our existing and published FAST-EM array tomography workflow for high-volume high-resolution mapping of WPBs in cultured endothelial cells.

Initial setup with endothelial cells (ECFCs) from healthy donors. When successful this will be extended to ECFCs derived from patients, e.g. with VWF trafficking defects (VWD, Storage pool disease, etc) and to ECs in which specific proteins of interest are depleted via shRNA or CRISPR targeting. You will then capture WPB trafficking events using fluorescence-guided high resolution EM imaging. WPBs and endolysosomal organelles will be labeled using fluorescent reporters or fluorophore-labeled antibodies. Finally, after succesful EM, you will work on segmentation, annotation and analysis of organelles in endothelial cells. We will train a convolutional neural network (based on U-net, e.g. similar to MitoNet that we used before on FAST-EM data) to automatically segment organelles from FAST-EM imaging data, with a focus on WPBs, endolysosomal compartments and vesicles of the ER-Golgi pathway. While you are expected to be actively involved in all aspects of the researc, expertise and support for all steps of sample preparation, EM acquisition and data reconstruction, and segmentation is available in both groups via technicians and PhD student on related projects.

Job requirements
You are a highly motivated and talented researcher with a strong interest in electron microscopy for life sciences and the development and application of novel methodology. You enjoy working in a multi-disciplinary environment at the interface of bio-medical research and instrument development and innovation, implementing new techniques to achieve tangible results. Embracing the opportunity to work with leading industrial partners, you know how to collaborate and achieve meaningful results geared to the development of pragmatic applications. You also put your curiosity to good use: you don’t take anomalies for granted and take the initiative to dig deeper and spar with experts. Harnessing your communication skills, you convince colleagues at TU Delft and Delmic of your approach, models and programs. And you enjoy interacting with and coaching talented bachelor and master students, while expanding your own knowledge and competencies.

You also have:

• PhD degree in Molecular Biology, (Applied) Physics, or a closely related field.
• Demonstrable skills in electron microscopy for life sciences, such as cellular EM, volume EM, or cryo-EM.
• A solid understanding and proven expertise in Python and the use of computational techniques, preferably neural networks, for data analysis and segmentation.
• Excellent communiction skills, connecting easily with people of diverse scientific backgrounds and being able to bridge research groups at two different locations.
• A proactive and curious mindset, with the ability to explore complex problems independently and collaboratively.
• A good command of spoken and written English, as you’ll be working in an internationally diverse community. You will also write scientific articles and your dissertation in English and participate in English-taught courses.
• An enthusiasm for coaching bachelor, master, and PhD students, and for presenting your work in scientific articles and international conferences.

TU Delft (Delft University of Technology)
Delft University of Technology is built on strong foundations. As creators of the world-famous Dutch waterworks and pioneers in biotech, TU Delft is a top international university combining science, engineering and design. It delivers world class results in education, research and innovation to address challenges in the areas of energy, climate, mobility, health and digital society. For generations, our engineers have proven to be entrepreneurial problem-solvers, both in business and in a social context.

At TU Delft we embrace diversity as one of our core values and we actively engage to be a university where you feel at home and can flourish. We value different perspectives and qualities. We believe this makes our work more innovative, the TU Delft community more vibrant and the world more just. Together, we imagine, invent and create solutions using technology to have a positive impact on a global scale. That is why we invite you to apply. Your application will receive fair consideration.

Challenge. Change. Impact!

Faculty Applied Sciences
With more than 1,100 employees, including 150 pioneering principal investigators, as well as a population of about 3,600 passionate students, the Faculty of Applied Sciences is an inspiring scientific ecosystem. Focusing on key enabling technologies, such as quantum- and nanotechnology, photonics, biotechnology, synthetic biology and materials for energy storage and conversion, our faculty aims to provide solutions to important problems of the 21st century. To that end, we educate innovative students in broad Bachelor's and specialist Master's programmes with a strong research component. Our scientists conduct ground-breaking fundamental and applied research in the fields of Life and Health Science & Technology, Nanoscience, Chemical Engineering, Radiation Science & Technology, and Engineering Physics. We are also training the next generation of high school teachers.

Click here to go to the website of the Faculty of Applied Sciences.

PhD Position Zeolites for PFAS Removal from Concentrated Waste Streams

Job description

Poly- and Perfluoralkyl substances (PFAS) are man-made persistent chemical compounds and have a negative effect on the environment and public health, due to their toxicity at very low concentrations. To remove low concentrations of organic micropollutants (OMPs) such as PFAS from water, nano- or reverse osmosis membrane technologies are increasingly considered and/or implemented by drinking water treatment plants. While such membranes produce safe drinking water, they also produce substantial volumes of highly concentrated waste streams (>5-fold higher PFAS concentrates than the treated water) that cannot be discharged directly without treatment. High-silica zeolites can selectively remove PFAS and other OMPs from such complex concentrates, and are potentially more effective than conventional activated carbon for PFAS removal when applied to concentrated waste streams. Previous research at TU Delft and elsewhere has already shown fast kinetics and high capacity for OMPs on zeolites in water with competing ions and organic compounds. The next-generation adsorbents we aim to develop should have (i) a higher affinity for OMPs, including short-chain PFAS, and (ii) a lower affinity for salts and organic matter, to minimize competition with OMP removal. In addition, to maximize re-use and longevity these adsorbents should also allow for (iii) frequent and (iv) effective regeneration.

This PhD is embedded in the recently funded NWO Perspektief project BlueVantage, connecting a diverse group of academics and societal stakeholders to inform safe and circular water (re)use across the water sector. You will be supervised by adsorption researchers from TU Delft and Wageningen University & Research (WUR). Our academic partners and our industrial project partner will produce tailored high-silica zeolites for your research.

You will take on the challenge to explore the selectivity of next-generation adsorbents for PFAS and adsorbent regeneration. You will:

• Drive and inform the design and selection of high-silica zeolites based on literature.
• Design experiments to test adsorbent materials with the goal of understanding performance and adsorption mechanisms for the target pollutants.
• Explore laboratory data using statistics and adsorption models to understand underlying trends, explore adsorption mechanisms and predict performance.
• Investigate loading and regeneration in lab experiments and potential pilot installations.
• Hold close feedback loops with industrial and academic partners.

The position is offered by Dr. Kim Lompe and promoter Prof. Dr. Luuk Rietveld at TU Delft and Dr. Gabriel Sigmund at WUR. All three will provide their specific expertise in adsorption and water treatment.

Job requirements
Need-to-have:

• A Master's degree in Water Treatment, Environmental Engineering or related field.
• Laboratory skills for basic water analysis.
• Data analysis skills for statistical analysis and data visualization and willingness to improve these.
• Initiative and engineering spirit to solve problems hands-on.
• Good communication skills to communicate with supervisor and colleagues.
• English Proficiency Test IELTS of 7.0 (scores of at least 6.5 in all sections) or TOEFL of 100 (scores of at least 21 for all sections). For more details please check the Graduate Schools Admission Requirements.

Nice-to-have:

• Experience working with adsorption materials.
• Programming skills (e.g. Python or R).

TU Delft
Delft University of Technology is built on strong foundations. As creators of the world-famous Dutch waterworks and pioneers in biotech, TU Delft is a top international university combining science, engineering and design. It delivers world class results in education, research and innovation to address challenges in the areas of energy, climate, mobility, health and digital society. For generations, our engineers have proven to be entrepreneurial problem-solvers, both in business and in a social context.

At TU Delft we embrace diversity as one of our core values and we actively engage to be a university where you feel at home and can flourish. We value different perspectives and qualities. We believe this makes our work more innovative, the TU Delft community more vibrant and the world more just. Together, we imagine, invent and create solutions using technology to have a positive impact on a global scale. That is why we invite you to apply. Your application will receive fair consideration.

Challenge. Change. Impact!

The Faculty of Civil Engineering & Geosciences
The Faculty of Civil Engineering & Geosciences (CEG) is committed to outstanding international research and education in the field of civil engineering, applied earth sciences, traffic and transport, water technology, and delta technology. Our research feeds into our educational programmes and covers societal challenges such as climate change, energy transition, resource availability, urbanisation and clean water. Our research projects are conducted in close cooperation with a wide range of research institutions. CEG is convinced of the importance of open science and supports its scientists in integrating open science in their research practice. The Faculty of CEG comprises 28 research groups in the following seven departments: Materials Mechanics Management & Design, Engineering Structures, Geoscience and Engineering, Geoscience and Remote Sensing, Transport & Planning, Hydraulic Engineering and Water Management.

Click here to go to the website of the Faculty of Civil Engineering & Geosciences.

PhD Position Ultrafast Photoacoustic Imaging

Job description

Ultrafast photoacoustics is a process in which we use extremely short laser pulses to heat a material, giving rise to a rapid expansion that results in the generation of high-frequency ultrasound waves. We have developed methods to detect such ultrasound waves using light as well, enabling optical microscopy with ultrasound as a contrast agent.

In this project, you will build a microscope based on this photoacoustics concept. Working as part of a small team of researchers, you get to design and develop the imaging system, and combine it with the ultrafast photoacoustics system available in the group. In addition to optics and microscopy, the experiments involve femtosecond lasers, electronic synchronisation systems, and sensitive data acquisition methods such as lock-in detection. You will then apply this novel microscope to study the mechanical properties of microscopic objects, such as semiconductor devices and biological cells. Data analysis and interpretation of the measured signals to transform them into 3D images will be another important challenge. As the propagation of sound depends on material properties such as density and stiffness, this microscope will give you a unique capability to visualize local material properties inside complex microstructures.

You will be part of the Optics for Nanoscale Metrology team, in the Optics cluster of the department of Imaging Physics at TU Delft. In this team, consisting of several PhD students, postdocs and undergraduates, we focus on developing new concepts for 3D imaging of nanostructures, using light.

Job requirements

• A masters degree in Physics or a related subject
• Strong affinity with experimental research in optics, lasers, imaging/microscopy and or time-resolved spectroscopy
• Good communication skills (verbal and written) in English are required
• Strong analytical skills, critical thinking, and a creative approach to problem solving
• Ability to work in a multidisciplinary team as well as individually

TU Delft (Delft University of Technology)
Delft University of Technology is built on strong foundations. As creators of the world-famous Dutch waterworks and pioneers in biotech, TU Delft is a top international university combining science, engineering and design. It delivers world class results in education, research and innovation to address challenges in the areas of energy, climate, mobility, health and digital society. For generations, our engineers have proven to be entrepreneurial problem-solvers, both in business and in a social context.

At TU Delft we embrace diversity as one of our core values and we actively engage to be a university where you feel at home and can flourish. We value different perspectives and qualities. We believe this makes our work more innovative, the TU Delft community more vibrant and the world more just. Together, we imagine, invent and create solutions using technology to have a positive impact on a global scale. That is why we invite you to apply. Your application will receive fair consideration.

Challenge. Change. Impact!

Faculty Applied Sciences
With more than 1,100 employees, including 150 pioneering principal investigators, as well as a population of about 3,600 passionate students, the Faculty of Applied Sciences is an inspiring scientific ecosystem. Focusing on key enabling technologies, such as quantum- and nanotechnology, photonics, biotechnology, synthetic biology and materials for energy storage and conversion, our faculty aims to provide solutions to important problems of the 21st century. To that end, we educate innovative students in broad Bachelor's and specialist Master's programmes with a strong research component. Our scientists conduct ground-breaking fundamental and applied research in the fields of Life and Health Science & Technology, Nanoscience, Chemical Engineering, Radiation Science & Technology, and Engineering Physics. We are also training the next generation of high school teachers.

Click here to go to the website of the Faculty of Applied Sciences.