PhD candidate; protein transport across the unique mycobacterial outer membrane

We are looking for an enthusiastic and motivated PhD candidate to join Dr. Edith Houben's team in the Molecular Microbiology Section of the Amsterdam Institute for Life and Environment (A-LIFE).

Your function

All bacteria depend on extracellular proteins to be able to communicate and interact with their environment. A particular biological challenge is to get these relatively large molecules from the cytosol across the surrounding multi-layered bacterial cell envelope without compromising its integrity, which is crucial for cell functioning. This challenge is even more exceptional for mycobacteria, as they have a specialized and highly impermeable outer membrane in addition to a cytoplasmic membrane. For pathogenic mycobacteria, such as the deadliest human bacterial pathogen Mycobacterium tuberculosis, the extreme hydrophobicity and impermeability of this outer membrane is essential to resist killing by our immune system, while also providing intrinsic resistance to many antibiotics. Nevertheless, pathogenic mycobacteria, like all other bacteria, strictly rely on the export of proteins for their physiology and virulence. To reconcile these two conflicting properties, mycobacteria have evolved a number of specialized protein transport machineries called type VII secretion systems (T7SSs). While we have gained important insight into the channel mediating protein transport across the cytoplasmic membrane (Bunduc et al., Nature 593:445-448), the mechanism of protein transport across the second mycobacterial membrane remains unknown. Unravelling the outer membrane part of the T7SSs could reveal them as weak spots in the impermeable mycobacterial cell envelope that can be exploited for the development of new antibiotics.

You will study how T7SSs are able to transport proteins across the special mycobacterial outer membrane, using recently acquired data on the central role of specific T7SS substrates in this process. You will assess the subcellular location and interactions of these proteins, characterize their biochemical and structural properties, and determine their roles in virulence. For this, you will learn and use a wide range of state-of-the-art genetic and protein chemistry approaches, combined with advanced mass spectrometry, structural analysis, high-resolution fluorescence microscopy and infection experiments.

The planned starting date for the project is between April and June 2024.

Your profile

  • MSc-degree in biology, biomedical sciences, life sciences or a related discipline (also candidates close to graduating are encouraged to apply)
  • Strong motivation to pursue a research career
  • Theoretical knowledge of microbiology, bacterial genetics and protein science
  • Practical experience in molecular biology and/or protein chemistry
  • English conversation, writing skills, and presentation skills

As a university, we strive for equal opportunities for all, recognising that diversity takes many forms. We believe that diversity in all its complexity is invaluable for the quality of our teaching, research and service. We are always looking for talent with diverse backgrounds and experiences. This also means that we are committed to creating an inclusive community so that we can use diversity as an asset.

We realise that each individual brings a unique set of skills, expertise and mindset. Therefore we are happy to invite anyone who recognises themselves in the profile to apply, even if you do not meet all the requirements.

What do we offer?

A challenging position in a socially engaged organisation. At VU Amsterdam, you contribute to education, research and service for a better world. And that is valuable. So in return for your efforts, we offer you:

  • a salary of € 2.770,00 (PhD) and maximum € 3.539,00 (PhD) gross per month in the fourth year, for a full-time employment.
  • an employment contract of initially 1 year. If there is sufficient perspective, this will be extended to a total of 4 years. Your dissertation at the end of the fourth year forms the end of your employment contract.

We also offer you attractive fringe benefits and arrangements. Some examples:

  • A full-time 38-hour working week comes with a holiday leave entitlement of 232 hours per year. If you choose to work 40 hours, you have 96 extra holiday leave hours on an annual basis. For part-timers, this is calculated pro rata.
  • 8% holiday allowance and 8.3% end-of-year bonus
  • contribution to commuting expenses
  • space for personal development
  • discount on (and occasionally exclusive access to) theater performances and courses at the Griffioen Cultural Center

About us

Vrije Universiteit Amsterdam

Vrije Universiteit Amsterdam stands for values-driven education and research. We are open-minded experts with the ability to think freely. - a broader mind. Maintaining an entrepreneurial perspective and concentrating on diversity, significance and humanity, we work on sustainable solutions with social impact. By joining forces, across the boundaries of disciplines, we work towards a better world for people and planet. Together we create a safe and respectful working and study climate, and an inspiring environment for education and research. Learn more about our codes of conduct

We are located on one physical campus, in the heart of Amsterdam's Zuidas business district, with excellent location and accessibility.  Over 5,500 staff work at the VU and over 30,000 students attend academic education.

Diversity

Diversity is the driving force of the VU. The VU wants to be accessible and receptive to diversity in disciplines, cultures, ideas, nationalities, beliefs, preferences and worldviews. We believe that trust, respect, interest and differences lead to new insights and innovation, to sharpness and clarity, to excellence and a broader understanding. We stand for an inclusive community and believe that diversity and internationalisation contribute to the quality of education, research and our services.

Therefore, we are always searching for people whose backgrounds and experience contribute to the diversity of the VU community.

Faculty of Science

Researchers and students at VU Amsterdam’s Faculty of Science tackle fundamental and complex scientific problems to help pave the way for a sustainable and healthy future. From forest fires to big data, from obesity to malnutrition, and from molecules to the moon: we cover the full spectrum of the natural sciences. Our teaching and research have a strong experimentally technical, computational and interdisciplinary nature.

We work on new solutions guided by value-driven, interdisciplinary methodologies. We are committed to research, valorisation and training socially engaged citizens of the world who will make valuable contributions to a sustainable, healthy future.

Are you interested in joining the Faculty of Science? You will join undergraduate students, PhD candidates and researchers at the biggest sciences faculty in the Netherlands. You will combine a professional focus with a broad view of the world. We are proud of our collegial working climate, characterised by committed staff, a pragmatic attitude and engagement in the larger whole. The faculty is home to over 11,000 students enrolled in 40 study programmes. It employs over 1,600 professionals spread across 10 academic departments.

Amsterdam Institute for Life and Environment (A-LIFE)

A-LIFE brings together the groups of Molecular Microbiology, Systems Biology, Environment & Health, and Ecological Sciences, with the aim to advance the fundamental understanding of the interplay between life and its environment. A-LIFE seeks to connect properties and emergent behaviours across all scales, from molecules to ecosystems, including human populations. The research of the department covers a broad range of research topics, including ecology and evolution, microbiology, (eco)toxicology and analytical chemistry of pollutants, global change biology, and biotechnology, and the associated state-of-the-art methods and technologies, both computational and experimental.

The department is located in a new research building together with other biological, chemical and medical disciplines offering key research infrastructure and opportunities for collaboration. Part of the research in this building is clustered in the Amsterdam Institute of Molecular and Life Sciences (AIMMS; https://www.aimms.vu.nl/en/index.aspx).

The Molecular Microbiology section currently has 7 staff members and concentrates on the microbial cell envelope, protein secretion systems, novel antibiotics and phage biology (https://a-life-vu.nl/molecular-microbiology/).

Interested

Are you interested in this position and do you believe that your experience will contribute to the further development of our university? In that case, we encourage you to submit your application via the application button until 29/02/2024 and upload your documents including:

  • motivation letter
  • your CV (including your education history, short summary of Master thesis and other research experience, a list of peer-reviewed publications)
  • relevant diplomas
  • at least 2 reference contacts

PLEASE DO NOT APPLY THROUGH THE MAIL, only applications through the VU application system will be considered.

Acquisition in response to this advertisement is not appreciated.

Your function

All bacteria depend on extracellular proteins to be able to communicate and interact with their environment. A particular biological challenge is to get these relatively large molecules from the cytosol across the surrounding multi-layered bacterial cell envelope without compromising its integrity, which is crucial for cell functioning. This challenge is even more exceptional for mycobacteria, as they have a specialized and highly impermeable outer membrane in addition to a cytoplasmic membrane. For pathogenic mycobacteria, such as the deadliest human bacterial pathogen Mycobacterium tuberculosis, the extreme hydrophobicity and impermeability of this outer membrane is essential to resist killing by our immune system, while also providing intrinsic resistance to many antibiotics. Nevertheless, pathogenic mycobacteria, like all other bacteria, strictly rely on the export of proteins for their physiology and virulence. To reconcile these two conflicting properties, mycobacteria have evolved a number of specialized protein transport machineries called type VII secretion systems (T7SSs). While we have gained important insight into the channel mediating protein transport across the cytoplasmic membrane (Bunduc et al., Nature 593:445-448), the mechanism of protein transport across the second mycobacterial membrane remains unknown. Unravelling the outer membrane part of the T7SSs could reveal them as weak spots in the impermeable mycobacterial cell envelope that can be exploited for the development of new antibiotics.

You will study how T7SSs are able to transport proteins across the special mycobacterial outer membrane, using recently acquired data on the central role of specific T7SS substrates in this process. You will assess the subcellular location and interactions of these proteins, characterize their biochemical and structural properties, and determine their roles in virulence. For this, you will learn and use a wide range of state-of-the-art genetic and protein chemistry approaches, combined with advanced mass spectrometry, structural analysis, high-resolution fluorescence microscopy and infection experiments.

The planned starting date for the project is between April and June 2024.

Your profile

  • MSc-degree in biology, biomedical sciences, life sciences or a related discipline (also candidates close to graduating are encouraged to apply)
  • Strong motivation to pursue a research career
  • Theoretical knowledge of microbiology, bacterial genetics and protein science
  • Practical experience in molecular biology and/or protein chemistry
  • English conversation, writing skills, and presentation skills

As a university, we strive for equal opportunities for all, recognising that diversity takes many forms. We believe that diversity in all its complexity is invaluable for the quality of our teaching, research and service. We are always looking for talent with diverse backgrounds and experiences. This also means that we are committed to creating an inclusive community so that we can use diversity as an asset.

We realise that each individual brings a unique set of skills, expertise and mindset. Therefore we are happy to invite anyone who recognises themselves in the profile to apply, even if you do not meet all the requirements.

What do we offer?

A challenging position in a socially engaged organisation. At VU Amsterdam, you contribute to education, research and service for a better world. And that is valuable. So in return for your efforts, we offer you:

  • a salary of € 2.770,00 (PhD) and maximum € 3.539,00 (PhD) gross per month in the fourth year, for a full-time employment.
  • an employment contract of initially 1 year. If there is sufficient perspective, this will be extended to a total of 4 years. Your dissertation at the end of the fourth year forms the end of your employment contract.

We also offer you attractive fringe benefits and arrangements. Some examples:

  • A full-time 38-hour working week comes with a holiday leave entitlement of 232 hours per year. If you choose to work 40 hours, you have 96 extra holiday leave hours on an annual basis. For part-timers, this is calculated pro rata.
  • 8% holiday allowance and 8.3% end-of-year bonus
  • contribution to commuting expenses
  • space for personal development
  • discount on (and occasionally exclusive access to) theater performances and courses at the Griffioen Cultural Center

About us

Vrije Universiteit Amsterdam

Vrije Universiteit Amsterdam stands for values-driven education and research. We are open-minded experts with the ability to think freely. - a broader mind. Maintaining an entrepreneurial perspective and concentrating on diversity, significance and humanity, we work on sustainable solutions with social impact. By joining forces, across the boundaries of disciplines, we work towards a better world for people and planet. Together we create a safe and respectful working and study climate, and an inspiring environment for education and research. Learn more about our codes of conduct

We are located on one physical campus, in the heart of Amsterdam's Zuidas business district, with excellent location and accessibility.  Over 5,500 staff work at the VU and over 30,000 students attend academic education.

Diversity

Diversity is the driving force of the VU. The VU wants to be accessible and receptive to diversity in disciplines, cultures, ideas, nationalities, beliefs, preferences and worldviews. We believe that trust, respect, interest and differences lead to new insights and innovation, to sharpness and clarity, to excellence and a broader understanding. We stand for an inclusive community and believe that diversity and internationalisation contribute to the quality of education, research and our services.

Therefore, we are always searching for people whose backgrounds and experience contribute to the diversity of the VU community.

Faculty of Science

Researchers and students at VU Amsterdam’s Faculty of Science tackle fundamental and complex scientific problems to help pave the way for a sustainable and healthy future. From forest fires to big data, from obesity to malnutrition, and from molecules to the moon: we cover the full spectrum of the natural sciences. Our teaching and research have a strong experimentally technical, computational and interdisciplinary nature.

We work on new solutions guided by value-driven, interdisciplinary methodologies. We are committed to research, valorisation and training socially engaged citizens of the world who will make valuable contributions to a sustainable, healthy future.

Are you interested in joining the Faculty of Science? You will join undergraduate students, PhD candidates and researchers at the biggest sciences faculty in the Netherlands. You will combine a professional focus with a broad view of the world. We are proud of our collegial working climate, characterised by committed staff, a pragmatic attitude and engagement in the larger whole. The faculty is home to over 11,000 students enrolled in 40 study programmes. It employs over 1,600 professionals spread across 10 academic departments.

Amsterdam Institute for Life and Environment (A-LIFE)

A-LIFE brings together the groups of Molecular Microbiology, Systems Biology, Environment & Health, and Ecological Sciences, with the aim to advance the fundamental understanding of the interplay between life and its environment. A-LIFE seeks to connect properties and emergent behaviours across all scales, from molecules to ecosystems, including human populations. The research of the department covers a broad range of research topics, including ecology and evolution, microbiology, (eco)toxicology and analytical chemistry of pollutants, global change biology, and biotechnology, and the associated state-of-the-art methods and technologies, both computational and experimental.

The department is located in a new research building together with other biological, chemical and medical disciplines offering key research infrastructure and opportunities for collaboration. Part of the research in this building is clustered in the Amsterdam Institute of Molecular and Life Sciences (AIMMS; https://www.aimms.vu.nl/en/index.aspx).

The Molecular Microbiology section currently has 7 staff members and concentrates on the microbial cell envelope, protein secretion systems, novel antibiotics and phage biology (https://a-life-vu.nl/molecular-microbiology/).

Questions about the vacancy?

Please contact

Edith Houben

Universitair Hoofddocent

Interested

Are you interested in this position and do you believe that your experience will contribute to the further development of our university? In that case, we encourage you to submit your application via the application button until 29/02/2024 and upload your documents including:

  • motivation letter
  • your CV (including your education history, short summary of Master thesis and other research experience, a list of peer-reviewed publications)
  • relevant diplomas
  • at least 2 reference contacts

PLEASE DO NOT APPLY THROUGH THE MAIL, only applications through the VU application system will be considered.

Acquisition in response to this advertisement is not appreciated.

Questions about the vacancy?

Please contact

Edith Houben

Universitair Hoofddocent

Application procedure

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