Mechanism of enzyme activation discovered

In an ISB effort the research groups lead by  Anna Linusson, Elisabeth Sauer-Eriksson and Magnus Wolf-Watz has discovered a key event in activation of the essential enzyme adenylate kinase. It was discovered that the large-scale and activating conformational change triggered by ATP binding is nucleated by a strong cation-PI interaction formed between the cationic sidechain of an arginine with the aromatic adenosine base of ATP. The discovery may pave way for future enzyme design efforts where recognition of aromatic systems is required. The finding was made possible through an integrative effort using DFT calculations, NMR spectroscopy and x-ray crystallography. The team consisted of Per Rogne, David Andersson, Christin Grundström, Elisabeth Sauer-Eriksson, Anna Linusson and Magnus Wolf-Watz. The finding is published in Biochemistry https://pubs.acs.org/doi/10.1021/acs.biochem.9b00538.

PhD position in Karina Persson’s group

A fully funded PhD position is available in Karina Persson’s group. The overall aim of the project is to obtain structural and functional data of bacterial fimbrial proteins and associated proteins involved in maturation of fimbria For more information and how to apply:

https://umu.mynetworkglobal.com/en/what:job/jobID:272296/

The closing date for applications is the 5th of Aug. 2019.

Postdoc position available in the Berntsson lab – study of adhesion proteins in G+ T4SSs

The Berntsson lab at the department of Medical Biochemistry and Biophysics at Umeå University, Sweden, is looking to recruit postdoctoral fellow (2-year fellowships, funded by the Kempe Foundation) to study the structural and functional aspects of Type 4 Secretion Systems. These large protein complexes are responsible for horizontal gene transfer between bacteria. As such, they facilitate the spread of, among other genes, antibiotic resistance between bacteria, both intra- and interspecies.

The overall goal of this project is to structurally and functionally characterize the adhesion proteins of G+ Type 4 Secretion Systems. These proteins are thought to be responsible for facilitating mating pair formation between the cells. We have the past years studied the T4SS from the pCF10 plasmid from Enterococcus faecalis, and we now understand the structural basis for how these cell-wall anchored proteins are involved both in biofilm formation and conjugation. However, there are numerous unanswered questions that we are still pursuing. The project will involve both functional assays in molecular biology, various biochemistry techniques (such as EMSAs and ITC) as well as protein structural determination via X-ray crystallography and/or single particle cryo EM. 

Qualifications

The applicants must possess a PhD, or another diploma deemed equivalent to a PhD, within molecular biology, biochemistry, structural biology or a related field. Furthermore, the applicant must have practical experience and expertise of cloning and protein production and purification in bacteria. The applicant must also have practical experience with either protein X-ray crystallography or cryo Electron Microscopy. Previous experience of working with Gram-positive bacteria is a merit. The applicants must have a very good level of English, both written and spoken. The applicants are also expected to be good team players, but should also be able to work independently. 

Application

The application should consist of the following:

  1. A motivation letter (max 1 A4), where you highlight why you want to join the laband study T4SSs. This letter must also include your contact information.
  2. The Curriculum Vitae of the applicant, including a list of published peer-reviewed articles.
  3. Copy of the PhD diploma (or equivalent).
  4. Contact details for three references, of which one should be your PhD supervisor.

The duration of the fellowship is 2 years. Your application should be written in English and prepared as a single package in PDF format, to be submitted to ronnie.berntsson@umu.se. Make sure touse the subject line: “postdoc application 2019-08” in the application email.Submit the applicationon August 19th, 2019 at the latest. The top ranked candidates will be contacted within two weeks from the closing date for an interview. Starting date according to agreement. For more information about the research or other details, do not hesitate to contact Dr. Ronnie Berntsson. 

Email: ronnie.berntsson@umu.se

Webpage: https://www.biostruct.umu.se/principal-investigators/ronnie-berntsson/

Postdoctoral program

We are happy to announce that the Kempe foundation is funding an ISB postdoc program with two fellowships 2019 and three fellowships 2020. Running costs are included for the positions. The program will fund new constellations that tackle interdisciplinary structural biology projects. For more information please go to the page ISB Postdoctoral program.

PhD position in the Andersson lab

We are seeking a PhD student in chemistry that will be part of a research team focused on understanding membrane protein transport using experimental techniques such as time-resolved X-ray scattering and biochemical assays, as well as computer simulation. Application deadline is 2019-06-03.

Project description
Biological membranes contain proteins that are necessary for all forms of Life – not least human beings. Development of structural characterization methods during the last 20 years has resulted in increased understanding of these membrane proteins, which in turn has increased production of new pharmaceuticals. We now face a major challenge – how can we take the next step and understand how proteins change their structures to perform their designated functions. By determining intermediate structures in the natural membrane environment, we could significantly increase the number of pharmaceutical targets. We will specifically characterize transport proteins in pathogenic bacteria, which are absent in humans, since such proteins are targets for development of new antibiotics that has potential to fight multi-drug resistance that pose a severe threat to humans, society, and health care.

Working tasks
The PhD student will be part of an existing research team that combines experimental methods and computer simulation to understand membrane protein transport. We have developed a combination of time-resolved X-ray scattering and computer simulation capable of determining transient intermediate states in the natural membrane environment. Our work is carried out on the absolute forefront of structural biology and will prepare the PhD student for a continued research career in academia or industry.

The PhD student will acquire a unique skillset with both experimental expertise and high-performance computing. The research spans molecular biology production and characterisation of proteins to development work at the synchrotrons MAXIV (Lund) and ESRF (Grenoble). The computer simulations will be performed on the national SNIC platform at the high-performance computing center HPC2N. The work will be performed within the context of Integrated Structural Biology (https://www.biostruct.umu.se) at Umeå University that provides seminar series as well as an exciting research environment.

Qualifications
To be admitted for studies at third-cycle level you are required to have completed a second-cycle level degree, or completed course requirements of at least 240 ECTS credits, of which at least 60 ECTS credits are at second-cycle level or have an equivalent education from abroad, or equivalent qualifications.

To fulfill the specific entry requirements to be admitted for studies at third-cycle level in chemistry, you are required to have completed first-cycle courses of at least 90 ECTS credits within the field of chemistry or another subject considered to be directly relevant to the specialization in question (such as physics, biology etc). Of those 90 ECTS credits, at least 15 ECTS credits shall have been acquired at second-cycle level within the specialization or an equivalent subject.

Good knowledge of the English language, both written and spoken, is required as well as a great interest within the field of biophysics and/or biochemistry. A suitable candidate must also be creative, have good collaboration skills, have a high degree of independence, and problem-solving analytical ability. Experience of protein production and characterization and/or Linux terminal/programming are considered as merits.

Terms of employment
The appointment aims at a PhD degree and the main task of the PhD student is to pursue their doctoral studies, which includes participation in research projects as well as postgraduate courses. In the assignments, teaching and other departmental work (up to a maximum of 20%) can be included. The employment is limited to four years full-time or up to five years when part-time teaching. The salary placement takes place according to the established salary level for doctoral employment.

Application
A complete application, written in English or Swedish, should contain a Curriculum Vitae, a cover letter including a description of your research interests and motivation for applying for this position, copies of degree certificates or equivalent, including documentation of completed academic courses and obtained grades, name and contact information of at least two reference persons.

Applications must be submitted via our e-recruitment system (link at https://www.umu.se/en/work-with-us/open-positions/phd-student-position-in-chemistry-with-focus-on-biophysical-chemistry_267035/). The last day to apply is 2019-06-03.

For more information about the research, position, or other details, please contact Docent Magnus Andersson
email: magnus.p.andersson@umu.se
webpage: https://www.biostruct.umu.se/principal-investigators/magnus-andersson/

About us
The Department of Chemistry is one of the largest departments within the Faculty of Science and Technology with approximately 200 employees, of which approximately 40 are PhD students, and constitutes a strong and expanding research environment. The Department has three major research areas: Biological Chemistry, Environmental and Biogeochemistry, and Technical Chemistry. We are also a strong partner in the Chemical-Biological Center (KBC), which provides excellent scientific infrastructure with several core facilities and technical platforms. You can find more information here: https://www.umu.se/en/chemical-biological-centre/. Information about the postgraduate education can be found on the Faculty of Science and Technology website: www.umu.se/en/faculty-of-science-and-technology/education/doctoral-studies/chemistry/. For more information about working at Umeå University, https://www.umu.se/en/work-with-us/.

Umeå University wants to offer an equal environment where open dialogue between people with different backgrounds and perspectives lay the foundation for learning, creativity and development. We welcome people with different backgrounds and experiences to apply for the current employment.

PhD Studentship available in the Berntsson lab

There is one open position for a fully funded PhD studentship available in the Berntsson lab. For further info and to apply, please see:

https://www.umu.se/en/work-with-us/open-positions/phd-studentship-with-focus-on-medical-biochemistrymedical-biophysics_261289/

Postdoctoral fellowships available in the Berntsson lab

The Berntsson lab at the department of Medical Biochemistry and Biophysics at Umeå University, Sweden, is looking to recruit up to two postdoctoral fellows (2-year fellowships, funded by the Kempe Foundation) to study the structural and functional aspects of Type 4 Secretion Systems. These large protein complexes are responsible for horizontal gene transfer between bacteria. As such, they facilitate the spread of, among other genes, antibiotic resistance between bacteria, both intra- and interspecies. 


The overall goals of these projects are to structurally and functionally characterize the DNA processing proteins of G+ Type 4 Secretion Systems. Parts of this project, for work on the T4SS from the pCF10 plasmid from Enterococcus faecalis, has already been started in the lab, but we are now also planning on expanding to other model systems. The projects will involve molecular biology, biochemistry and structural biology techniques, with an early emphasis on the functional characterization of these proteins and their complexes, followed by structural determination. 

Qualifications

The applicants must possess a PhD, or another diploma deemed equivalent to a PhD, within molecular biology, biochemistry, structural biology or a related field. Furthermore, the applicant must have practical experience and expertise of cloning and protein production and purification in bacteria. The applicant should preferably be experienced with functional studies of (membrane) proteins using various molecular biology and biochemical methods, such as ITC, SPR and fluorescence spectroscopy. Previous experience of working with gram-positive bacteria and membrane proteins is an advantage, as is previous experience of X-ray crystallography and electron microscopy. The applicants must have a very good level of English, both written and spoken. The applicants are also expected to be good team players, but should also be able to work independently. 

Application

The application should consist of the following:

  1. A motivation letter (max 1 A4), where you highlight why you want to join the lab and study T4SSs. This letter must also include your contact information.
  2. The Curriculum Vitae of the applicant, including a list of published peer-reviewed articles.
  3. Copies of the PhD diploma (or equivalent).
  4. Contact details for three references, of which one should be your PhD supervisor.

The Berntsson lab is part of the Integrated Structural Biology community at Umeå University, consisting of 14 research groups that use, and have access to, high-field NMR, X-ray crystallography (including regular synchrotron access), world-class cryoEM and computation biology with a high performance computing centre.


The duration of the fellowship is 2 years. Your application should be written in English and prepared as a single package in PDF format, to be submitted to ronnie.berntsson@umu.se. Make sure to use the subject line: “postdoc application 2019-04” in the application email. Submit the application on April 25, 2019 at the latest. The top ranked candidates will be contacted within three weeks from the closing date for an interview. Starting date according to agreement. For more information about the research or other details, do not hesitate to contact Ronnie Berntsson.

 
Email: ronnie.berntsson@umu.seWebpage: https://www.biostruct.umu.se/principal-investigators/ronnie-berntsson/

New Article in Cell Reports: Control of bacterial virulence through the peptide signature of the habitat

Krypotou, E., Scortti, M., Grundström, C., Oelker, M., Luisi, B.F., Sauer-Eriksson, A.E. & Vázquez-Boland, J. Control of bacterial virulence through the peptide signature of the habitat. (2019) Cell Reports, 26, 1815-1827.

We identify a major control mechanism of Listeria virulence based on antagonistic regulation by environmental peptides.Activity levels of the virulence regulator PrfA depend on the net balance between the rates of synthesis of the PrfA-activating cofactor GSH from exogenous peptide-derived cysteine and of direct, promiscuous PrfA inhibition by non-cysteine-containing peptides

New ISB Article by Erik Johansson et al in Nature Communications

Professor Erik Johansson has published an article in Nature Communications named “Structural consequence of the most frequently recurring cancer-associated substitution in DNA polymerase epsilon“. The study was a collaboration with Uppsala University and University of Nebraska Medical Center. The article can be found at: “www.nature.com/articles/s41467-018-08114-9”