PhD Position in Applying Cryo-Electron Tomography in Structural Neurobiology

Join the Institute for Chemical Neuroscience (iCNS) to study molecular changes in the human brain linked to psychiatric symptoms. In the brain, the complement system plays an important role in circuit homeostasis and disease.

Your job
iCNS aims to discover molecular changes in the human brain underlying psychiatric symptoms. In an NWO-supported Gravitation consortium, neurobiologists, chemists, psychiatrists and data scientists work closely together on the unique and well-documented human brain tissue from the Netherlands Brain Bank. Young scientists will be trained in combining chemistry, artificial intelligence and neurobiology. Ultimately, the interdisciplinary research from iCNS will lead to a molecular 'brain atlas' of psychiatric symptoms, and to new leads and approaches to improve the future diagnosis, prognosis and possible treatment of psychiatric disorders.

The innate complement system, which consists of more than thirty membrane-bound and secreted proteins, is an evolutionary old and highly conserved protein cascade system in the immune defense against pathogens and to remove damaged cells. In the brain, the complement system plays an important role in circuit homeostasis and disease. Complement is crucial in tagging and removing superfluous synapses on neurons and required for correct myelination of axons. When the activation and control mechanisms of complement fail, the dysregulation of cellular homeostasis may cause a delicate disbalance leading to tissue damage and diseases, including schizophrenia and depressive disorders.

This PhD project is part of a cross-disciplinary collaborative effort in the Institute for Chemical Neuroscience to develop new chemical tools and investigate complement pathways in the brain. Collectively, new insights into complement in psychiatry will be obtained, ranging from protein structure to functional consequences of complement dysfunctions. The work will deliver a basis for future research and biomarkers in neuropsychiatry.

You will join the Structural Neurobiology research group of Professor Bert Janssen, which combines biochemistry, X-ray crystallography and cryo-electron microscopy to unravel the molecular processes that facilitate cell-cell communication and interaction in the nervous system. As part of iCNS, you will collaborate with chemists and neurobiologists to make and improve molecular probes and visualise complement activity in the nervous system.

By joining our group, you will be part of an academic environment with several world-class scientists, Where English is the main language. You will get the opportunity to:

• develop skills in design of protein probes targeting specific complexes;
• produce and purify proteins in Escherichia coli and HEK293 cell cultures;
• determine structures of probe-target complexes with cryo electron microscopy;
• develop skills in cryo electron tomography on reconstituted enzyme complexes;
• learn how to apply cryo electron tomography to tagged organotypic slice cultures;
• gain deeper insights into the biology of neurons.

Develop academic skills such as effective scientific communication (written and oral), building collaborative networks and teaching. For example through our Molecular Life Sciences programme.

• A supportive environment with a commitment to academic development and maintaining a healthy work-life balance;
• a position for 18 months, with an extension to a total of four years upon successful assessment in the first 18 months;
• a gross monthly salary between €2,901 and €3,707 in the case of full-time employment (salary scale P under the Collective Labour Agreement for Dutch Universities (CAO NU));
• 8% holiday pay and 8.3% year-end bonus;
• a pension scheme, partially paid parental leave and flexible terms of employment based on the CAO NU.

In addition to the terms of employment laid down in the CAO NU, Utrecht University has a number of schemes and facilities of its own for employees. This includes schemes facilitating professional development, leave schemes and schemes for sports and cultural activities, as well as discounts on software and other IT products. We also offer access to additional employee benefits through our Terms of Employment Options Model. In this way, we encourage our employees to continue to invest in their growth. For more information, please visit Working at Utrecht University.

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You will work in the research group of Professor Bert Janssen, which is part of the Structural Biochemistry section. The group offers a collaborative environment, modern tools in structural biology; X-ray and cryo-electron microscopy and tomography, biochemical, biophysical and cell biological techniques and an extensive computing infrastructure for data processing. We have access to the in-house Electron Microscopy Centre, which houses advanced instrumentation for cryo-EM and cryo-ET, including a Talos Artica, equipped with K2 direct electron detector, energy filter and a Volta phase plate.

The Structural Biochemistry group is part of the Bijvoet Centre for Biomolecular Research which coordinates the Molecular Life Sciences PhD programme and offers regular seminars by scientists from all over the world, access to advanced courses and regular PhD evenings for PhD candidates and postdocs to present their work and enhance social cohesion within the Bijvoet Centre. The Bijvoet Centre comprises six research sections that form a collaborative environment focussing on elucidating the structure of the biomolecules that make up all living organisms. In addition, the Bijvoet Centre has a state-of-the-art Protein Research Centre that is equipped for protein production, purification and analysis.

Bert Janssen is a researcher at the Institute for Chemical Neuroscience (iCNS) in which chemists, neurobiologists, psychiatrists and data scientists work together to discover the molecular changes in the human brain underlying psychiatric symptoms.