The paper “Conformational dynamics of the human serotonin transporter during substrate and drug binding” is the work from Ingvar Möller’s PhD thesis, an outcome of a long-standing collaboration between Prof. Kasper Rand and Prof. Claus Løland (Molecular Neuropharmacology Group, Department of Neuroscience and Pharmacology). The human serotonin transporter (hSERT) is an important drug target in the treatment of multiple mental diseases, and is here studied by use of hydrogen/deuterium exchange mass spectrometry (HDX-MS). The published data provides insights into the conformational dynamics of hSERT in solution and how these dynamics are impacted by the binding of biologically relevant substrate and ions (5-HT, Na+, K+), and drug inhibitors, and may possibly contribute to the development of future drug strategies. The work furthermore highlights the applicability of using HDX-MS to study the dynamic structure-function relationship and drug binding of complex protein systems like the human membrane transport proteins.
The paper “A post-translational modification of human Norovirus capsid protein attenuates glycan binding” has been published in Nature Communications. Human norovirus evasion is dependent on the binding to histo blood group antigens (HBGAs) through highly conserved binding sites in the P-domain of the norovirus capsid protein VP1. In the present work, the P-domain is studied in its dimeric form, called the P-dimer. The results show that the spontaneous deamidation of asparagine 373 in the P-dimer, dramatically decrease the HBGA-binding affinity. This was a collaborative effort and Esben and Kasper from the group contributed with HDX-MS experiments on wildtype and deamidated P-dimer revealing changes in protein dynamics upon deamidation.
Thomas Pysik, a Ph.D. student from the group of Andreas Ladurner at Ludwig Maximilian University of Munich is visiting our group for two weeks. He is working together with Joana and Kasper about applying HDX-MS to study the interaction of interesting biological systems.
We are delighted to host Thomas, and hope he have plenty of change to discuss ideas, learn new techniques, explore and experience Copenhagen. We enjoy having you here Thomas!
This Friday the whole group went to our friendship group in Odense, Denmark. The group of Thomas Jørgensen i University of Southern Denmark (SDU). HDX-MS is the main research area of both our groups, so the day was full of knowledge sharing, networking, and fun times! After a shorter delay, the meeting was initiated by shorter and longer presentations, and finished with a interesting workshop! Afterwards there was dinner and networking to the early hours. And a sightseeing in the fairytale city Odense the next day!
Thank you very much to the group at SDU for hosting this awesome event. We are looking forward to hosting Thomas and his group next year!
In collaboration with Perdita Barran and Bruno Bellina at the University of Manchester and Jeff Brown at Waters Corporation, we have just published a Letter in Analytical Chemistry that shows that ultraviolet photodissociation (UVPD) at 213 nm proceeds without H/D scrambling.
The results demonstrate that UVPD can measure deuterium levels at single residue resolution in HDX-MS experiments. UVPD therefore appears to provide a powerful methods for increasing the spatial resolution of the HDX-MS method.
Working with lasers is exciting stuff, join the fun!
Last year Kasper was awarded a professorship with special responsibilities (Professor MSO), and today the official inauguration took place. Head and Department, Flemming Madsen and Vice Dean of Research, Kristian Helin, was responsible for the inauguration.
Afterward Kasper gave a talk about his previous, current, and future research, as well as, teaching and research supervision. It was followed by a nice reception.
It has been fantastic to see the group grow and develop the last years. And we all are looking forward to more great research and fun times!
A new publication in Molecular Cell has recently been published: “A Poly-ADP-Ribose Trigger Releases the Auto-Inhibition of a Chromatin Remodeling Oncogene”. The work provides new molecular understanding of the function of the ALC1 protein, which is involved in chromatin remodeling and cancer. This opens up for possibilities to possible target the ALC1 protein in cancer treatment.
The work is a collaboration with researchers at the Ludwig-Maximilians University München. Hari visited our lab and worked with Ingvar and Kasper on the HDX-MS experiments in the study. Ingvar is a joint second outher and Kasper is shared corresponding author on the paper.
The department also wrote a piece about paper here:
An article was recently published in the Danish popular science magazine “Aktuel Naturvidenskab”, written by Carsten R. Kjaer titled “Kan forståelsen af et enzym løfte humøret?” (Can the understanding of an enzyme lift the mood). The article is based on an ongoing research project based on the Technical University of Denmark, where our group and Kasper Rand is also participation with HDX-MS experiments. The project focuses on understanding the enzyme THP2, which is important for serotonin production in the brain. Serotonin is important to regulate the mood of people, and THP2 is therefore an interesting target for development of new drugs to treat depression.
Read the article here (Danish only):
Recently, we sadly had to say godbye to a lot of students graduating. This also includes Zeinab, who was awarded a Ph.D. degree after a succesful defense. We wish her all the best in her new job at the pharmaceutical company Novo Nordisk. We will miss you Zeinab!
Her project and presentation was called: “Advancing hydrogen/deuterium exchange mass spectrometry (HDX-MS) methodology for conformational analysis of biopharmaceuticals. The assessment committee at the defense was: Professors David Weis (Kansas), Thomas Jørgensen (Southern Denmark) and Camilla Foged (Copenhagen).
Esben got awarded the PhD title yesterday after a really nice presentation and defense. His PhD thesis was called: “Conformational Dynamics of the Sortilin Receptor and its Molecular Interactions with Natural Ligans and Modulating Antibodies Measured by Hydrogen/Deuterium Exchange Mass Spectrometry”. The project was done in collaboration with Søren Christensen from Lundbeck, with Kasper as the academic supervisor.
The assessment committee consisted of Michael Ploug (UCPH), Wolfgang Rist (Boehringer Ingelheim), and Morten S. Nielsen (Aarhus University).
Esben has been in the group for four years, doing both his MSc thesis project and PhD, and it has been an huge pleasure having him as a colleague Esben is soon starting as a Postdoc in Switzerland, and the project is in collaboration with Protein Analysis Group. So luckily it is not the time to say goodbye.
Esben and Kasper has recently published a paper in JBC in collaboration with the pharmaceutical company Lundbeck: “Conformational characterization of nerve growth factor-β reveals that its regulatory pro-part domain stabilizes three loop regions in its mature part”. Congratulations for the very nice publication.
The conformational impact of the NGF propart on the mature part was assessed using HDX-MS. The paper also include mapping of both N– and O-glycosylation sites on both the mature and propart of NGF.
Ingvar succesfully defended his PhD titled: Exploring the Conformation and Dynamics of Neurotransmitter:Sodium Symporters by Hydrogen-Deuterium Exchange Mass Spectrometry. He is the second to finish his PhD from Protein Analysis Group. It have been a huge pleasure working with Ingvar for the last years, and he will be missed.
The assessment committee consisted of: Thomas Jørgensen (University of Southern Denmark) and Ganesh Anand (National University of Singapore) who both are experts in HDX-MS, and chairman Osman Mirza (University of Copenhagen) who is an expert in membrane proteins.
Scientists working with mass spectrometry to study protein conformations went to Vienna in Austra for the 7th Symposium on Structural Proteomics. Ellie, Esben, and Kasper all participated giving either a talk or a poster talk. Ellie and Kasper furthermore organized an HDX-MS workshop on the first day.
It was a great way to meet peers in the field, be updated on the newest science and create new and maintain old connections.
The group went for a weekend trip to Kaspers summerhouse (team building weekend), which is beautifully located close to the water. It was a trip filled with hiking, food cooked on a bonfire, climbing in trees, fun times, and for the brave few bathing in the autumn cold Danish water. We have went once a year, and we are all looking forward to keeping this awesome tradition in place!
On the 15th of September, most members of the Protein Analysis Group joined the first ISBUC annual meeting in the GeoCenter, hosted by the Faculty of Science.
The programme consisted of several talks in state-of-the art topics in the Structural Biology fields. Pioneers in the area, like Andrea Musacchio, Zoe Fisher, Nicholas Taylor, Robert Feidenhansl’ and Martin Malmsteen honoured us by giving some talks on their current studies.
In between these talks, many other scientists had the chance to participate in flash-talks and present some of their recent work as well.
Lunchtime allowed us all to socialize and share experiences, connecting all the people with the shared interest in Structural Biology.
At the end of the meeting, prizes for best student poster and best PhD/Group poster were given and snacks and drinks were generously distributed.
The day ended with some rain, but the scientific spirits were rising to the top after such a refreshing, mind-opening event!
We are all very excited to have you all on board and we are looking forward to working with you and getting to know you!
The group participated in this year’s DHL 5x5k relay run, and got the fastest team in the department. Great job everyone!
It was a great afternoon and evening the running, socializing, food, and drinks! We have participated every year and we are of course back next year as well.
The group recently co-authored two publications in collaboration with Statens Serum Institut, Radbound University, and Bioneer regarding development of novel malaria vaccine candidates. The chimeric fusion proteins combine epitopes of key malaria parasite antigens including the highly disulphide-bonded Pfs48/45 antigen, and are potential candidates for a multi-stage malaria vaccine that targets both the mosquito and human life-cycle stages of the parasite.
Work has been done optimizing expression, refolding, purification as well as analysis and characterization of the protein antigens. A detailed mapping of the cysteine connectivity of the Pfs48/45 antigen was performed by mass spectrometry as well.
ASMS is the biggest conference about mass spectrometry in the world with 384 scientific talks and over 2700 poster presentations. Kasper, Jens, Ulrik, Esben, and Anne Kathrine went to Indianapolis the 2.-8. June 2017. Jens, Ulrik and Esben presented posters about their work and Anne Kathrine gave a talk about her research in the “Membrane Proteins” session.
ASMS was a great opportunity to hear about the newest and most exciting research in mass spectrometry as well as great networking possibilities. There was also time for exploring the city and trying the local food and drinks. The group is already looking forward to ASMS 2018, this time in San Diego!
Today the first PhD student graduated from the group, after successfully defending the PhD. The title of the project was “Probing the Structural Dynamics of Membrane Proteins by Hydrogen/Deuterium Exchange Mass Spectrometry”.
The assessment committee consisted of: Prof. Poul Nissen from Aarhus University, an expert in membrane protein. Prof David Schriemer from University of Calgary, an expert in mass spectrometry based techniques including HDX-MS. And chairman Marco van de Weert from the department, who is an expert in various techniques for assessing protein structure and stability.
On the picture Patrick is flanked by his supervisors Kasper and Claus Løland and the PhD assessment committee on the left, Marco van de Weert, Poul Nissen and David Schriemer.
It has been a great pleasure having Patrick in the group, but we will keep in touch!
The 1st International Conference on Hydrogen Deuterium Exchange Mass Spectrometry (IC HDX) took place in Gothenburg, Sweden. 150 people with a strong interest in HDX-MS from both industry and academia joined for the workshop and the conference. Kasper was co-organizing the conference, but also Ellie, Esben, Gerard, Rasmus and Ulrik from the group participated. And Kasper, Esben and Ulrik gave a presentation at the conference.
It was great to see to many peers and experts in the field of HDX-MS to come together and exchange ideas and share experience. We are already looking forward to the next IC HDX conference in 2019, this time in Canada!
Three members of the group, Esben, Anne-Katrine and Ulrik participated in the Structural Mass Spectrometry Workshop in Rehovot, Israel. The week included great talks from leading experts in the field of native MS, ion mobility, HDX-MS, crosslinking and modelling of structural MS data. But the week was also filled with a trip to the old city Jaffa for dinner, poster presentations, lots of great local food, networking activities as well as a trip to the dead sea, Masada and Ein Gedi. Esben and his group also won an award for a structural MS based solution to a biological problem.
All in all it was a great workshop with perfect weather!
Eleanor, Jens, Ulrik and Kasper went to the annual Executive Seminar in Analytical Chemistry (ESAC), which took place in Copenhagen at the Scandic Hotel on the 26 April. It was a great way to keep updated on emerging topics and to network with analytical scientists in Denmark.
Kasper did a presentation titled “Studying the conformation and dynamics of membrane proteins through hydrogen/deuterium exchange and mass spectrometry” in the Life Scieence/Biotech session.
Eleanor Dickinson recently joined the group as a postdoc. She will work primarily with hydrogen/deuterium exchange mass spectrometry to study intrinsically disordered proteins.
She recently finished her Ph.D. in the Perdita Barran Group at the University of Manchester.
We are so happy to have Ellie in the group!
Hard working members of the Protein Analysis Group and the Microscale Analytical Systems Group are celebrating Easter with a burger lunch at Halifax.
Rasmus, Nanna, Tam, Henrik and Kasper have recently published a paper in the scientific journal Analytical Chemistry, titled: “Thiol-ene Monolithic Pepsin Microreactor with a 3D-Printed Interface for Efficient UPLC-MS Peptide Mapping Analyses”.
The work was done in collaboration with the Microscale Analytical Systems Group.
Ulrik was awarded with the EliteForsk-rejsestipendium (Elite research travel grant). The 200.000 DKK grant is awarded to enable very talented PhD students to carry out longer research stays at the best research environments world-wide. Ulrik will use to visits labs in Oxford and Manchester and to join international conferences. The grant was awarded by Crown Princess Mary and minister Søren Pind on behalf of the Ministry of Higher Education and Science.
Congratulations to Ulrik!
Zeinab and Kasper have together with collaborators from Biogen, published an article in Journal of The American Society for Mass Spectrometry.
A customized HDX-MS method was developed to inform on the structure of therapeutic proteins at very high concentrations (>100 mg/ml). This method enables analysis of the higher-order structure of the protein in the high-concentration formulation without prior dilution, and will potentially optimize development of highly concentrated formulations of protein drugs at low volumes. High concentration formulation of proteins could possible enable advantageous subcutaneous injections.
Kasper and Pernille have published a paper in MCP “A two-pronged binding mechanism of IgG to the neonatal Fc receptor controls complex stability and IgG serum half-life“.
Using HDX-MS and affinity chromatography they have studied the binding interactions of the neonatal Fc receptor (FcRn) and the IgG briakinumab. Correlate the occurrence of excessive FcRn binding to an unusually strong Fab-FcRn interaction and therefore the unusually short half-life of briakinumab.
There are four Ph.D. positions available in the group. The application deadline is: 28 February 2017. Read more about the positions and application procedures at http://www.vadema.eu/
We are looking forward to welcoming the new members to the group!
The group hosted Thomas Jørgensen and his group for the 1st Annual Jørgensen/Rand Group (H/D) Exchange Meeting.
The one-day event included six scientific presentations from each group, a lab tour, and a workshop regarding HDX-MS and a social dinner afterwards.
We are already looking forward to the event next year in Odense!
We had the great pleasure of having Shane Chandler (Benesch Group, Oxford) to join the group for two weeks.
Shane was working with gas-phase HDX-MS together with Ulrik and Kasper. It was two very productive and interesting weeks with many for knowledge sharing, idea creation and fruitful discussions.
The Danish weather was warm and sunny. So even if it was two busy weeks with a lot of work done in lab, Shane still had the opportunity to experience the city in the summer time.
It was a great pleasure of hosting Shane!