PhD Project in Structural Determination of Macromolecules

Chemistry is, with approximately 200 employees, one of the largest departments at the Faculty of Science at Stockholm University.

A significant part of the teaching activities takes place at the undergraduate level with courses in fundamental physical, inorganic, organic, and analytical chemistry. Teaching at the advanced level focuses on master's programs in sustainable chemistry, organic chemistry, and analytical chemistry.

Research activities at the department primarily involve studies of materials, including various classes such as ceramics, glass, porous materials, and soft materials. Projects often include synthesis and characterization using various methods; X-ray, neutron diffraction, electron microscopy, solid-state NMR, and computer modeling of materials with potential for various applications. Research activities within analytical chemistry focus on developing advanced analytical techniques for studying organic compounds and biomolecules. More information about us can be found here (https://www.su.se/institutionen-for-material-och-miljokemi/).

Project Description

Project Title: Development of Methods for Nano-Crystalline Fungi by Combining Metal-Organic Frameworks and 3D Electron Diffraction

Supervisors (PI): Prof. Xiaodong Zou (main supervisor), Dr. Gerhard Hofer (co-supervisor)

Determining the 3D atomic structures of macromolecules is crucial for understanding their biological functions and the chemical processes they govern. This information is also vital for drug design. X-ray diffraction remains the primary method for structure determination, but it requires large single crystals. 3D electron diffraction (3D ED), also known as MicroED, has proven to be a powerful technique for determining atomic structures from nano- and microcrystals that are too small for traditional methods. Its significance was highlighted in 2018 when it was featured by Science as one of the year's top ten breakthroughs (link (https://vis.sciencemag.org/breakthrough2018/)). Recently, Professor Zou's group developed innovative methods for crystallizing micro- and nanocrystals of proteins, as well as workflows for serial electron diffraction (SerialED). These workflows enabled automated screening of tens of thousands of crystals per hour, allowing for high-resolution and high-quality structural analyses of protein crystals. The advancements have made it possible to accurately determine atomic positions of ligands within protein molecules and analyze detailed protein-ligand interactions. These breakthroughs open new opportunities for the use of electron diffraction for structure-based and fragment-based drug design, providing unique insights and tools for drug development.

The PhD project focuses on applying and further developing the serial electron diffraction method to determine 3D protein structures and study protein-ligand interactions.

The project will include:

• Optimizing crystallization conditions for micro- and nanocrystals.
• Testing and improving workflows for data collection and processing for protein structure analysis with SerialED.
• Developing high-throughput ligand screening strategies for SerialED.
• Applying these new strategies to study protein-ligand interactions and identify potential drugs.

The candidate will collaborate with biochemists, structural biologists, and software developers at Stockholm University, SciLifeLab, and internationally leading laboratories. Opportunities exist to work with leading pharmaceutical companies such as AstraZeneca.

The project is funded by the Swedish Research Council (VR) and the Knut and Alice Wallenberg Foundation (KAW). More information about the project and Professor Xiaodong Zou can be found at this link (https://kaw.wallenberg.org/en/research/revolutionary-close-ups-building-blocks-life) and Professor here (https://www.su.se/profiles/xzou-1.187418).

Eligibility Requirements

To be admitted to doctoral education, the applicant must have basic and specific eligibility. The eligibility must be fulfilled by the application deadline.

Basic eligibility is achieved if you have completed a master's degree or fulfilled course requirements of at least 240 higher education credits (hp), of which at least 60 hp at the advanced level, or otherwise acquired equivalent knowledge within or outside the country.

Specific eligibility is described at this link (https://www.su.se/institutionen-for-material-och-miljokemi/forskning/b%C3%B6rja-forska).

Selection

Selection among applicants is made with regard to the ability to benefit from education at the doctoral level. Criteria used to assess this ability include:

• documented subject knowledge relevant to the research area
• analytical and creative thinking
• initiative
• independence
• collaborative ability
• ability to express oneself in spoken and written English.

Experience in biochemistry, structural biology, crystallography, and/or cryo-EM is advantageous.

More information can be found at this link (https://medarbetare.su.se/vart-su/styrning/regelboken/utbildning/antagningsordning-for-utbildning-pa-forskarniva).

About the Position

We offer a fixed-term position as a PhD student according to Chapter 5 of the Higher Education Ordinance (1993:100). The employment period may not exceed what corresponds to full-time doctoral education for four years. As a PhD student, you will primarily focus on your own doctoral education, but the position may also include limited work in education, research, and administration (maximum 20%).

A new PhD position is valid for a maximum of one year, and the position is renewed thereafter for a maximum of two years at a time.

Stockholm University is committed to being a workplace free from discrimination and providing equal rights and opportunities for all.

Contact

Further information can be obtained from Professor Xiaodong Zou, [email protected] (mailto:[email protected]). General information about the workplace, Kemikum at Stockholm University, can be obtained from the head of department, Professor Niklas Hedin, [email protected] (mailto:[email protected]).

Application

You apply for the PhD position via Stockholm University's recruitment system. Attach a personal letter and CV as well as the requested documents in the application form. You, as the applicant, are responsible for ensuring that the application is complete in accordance with the advertisement and that it reaches the university by the application deadline.

Instructions for applicants can be found on the website: this link (https://www.su.se/om-universitetet/jobba-p%C3%A5-su/att-s%C3%B6ka-en-anst%C3%A4llning).

Stockholm University contributes to the development of a sustainable democratic society through knowledge, enlightenment, and the pursuit of truth.