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Welcome to the Hamburg Structural Biology Meeting!
We are thrilled to invite you to the very first iteration of the Hamburg Structural Biology Meeting, where the best and brightest minds from our northern community come together to collaborate, innovate, and celebrate our shared passion for structural biology.
Look forward to a day at DESY filled with insightful talks, lively discussions, and the chance to make meaningful connections with colleagues from across the campus. Whether you're a Super Trouper in your field or just starting your journey, this is your opportunity to share your knowledge, learn from others, and discover new ways to support each other's work.
The rythm of the day is set by the following sessions:
The day will be wrapped up with a delightful BBQ at CFEL in the evening, because When All is Said and Done, we believe in fostering not just professional, but also personal connections.
Don't miss your chance to help shape the future of structural biology on our campus. Together, we can spark new ideas and build a collaborative environment that elevates us all. Join us for a day of inspiration and connection – let's make this a meeting to remember!
P.S. No need to show up in ABBA costumes - but if you feel like channeling your inner Dancing Queen, we won't stop you!
Welcome and introduction to the general idea of the meeting.
Afterwards, one person from each group will introduce the whole group with one slide: group photo, skills/equipment to offer, general aims.
Slides will be controlled by session chair, presenting group members should stand up.
Early career scientists wil present their projects focusing on prolems/issues/challenges. Attending (senior) scientists should give their opinion, ideas, suggestions in the following discussion round.
Presentation 15 min, Discussion 5 min
The family of the beta coronaviruses has caused multiple sever outbreaks like SARS, MERS and recently COVID. Due to their high mutation rates, it is likely that they cause further outbreaks in the future. They share a conserved 3C-like main protease (MPro) which is vital for its replication, making it an interesting drug target. To better understand this crucial enzyme, my project is about resolving the mechanism of SARS-CoV-2 MPro. I am trying to utilizing the time-resolved serial beamline P14-2 (TREXX) and the Spitrobot, a cryotrapping device, to trap intermediates along the reaction pathway.
Here we demonstrate preliminary results on the structural studies of human pre-Haptoglobin-2. We have established protocols to recombinantly produce pre-haptoglobin-2 and biophysically characterised it using various methods. Recombinant pre-haptoglobin-2 and its glycosylation sites have been verified by MS. Furthermore, Small-Angle X-rays Scattering (SAXS) has been employed for acquiring a low resolution structural model of the protein and its oligomeric assembly. We have produced mutants that do not process further to mature haptoglobin as well as mutants that cannot form higher oligomers. The aforementioned mutants lacking the ability to form higher oligomers have been performed in varied crystallization trials whereas no crystals have been obtained.
The family of the beta coronaviruses has caused multiple sever outbreaks like SARS, MERS and recently COVID. Due to their high mutation rates, it is likely that they cause further outbreaks in the future. They share a conserved 3C-like main protease (MPro) which is vital for its replication, making it an interesting drug target. To better understand this crucial enzyme, my project is about resolving the mechanism of SARS-CoV-2 MPro. I am trying to utilizing the time-resolved serial beamline P14-2 (TREXX) and the Spitrobot, a cryotrapping device, to trap intermediates along the reaction pathway.
Mycobacterium abscessus expresses an ADP-ribosyltransferase (ARR) responsible for the inactivation of rifampicin, a commonly used first-line antibiotic to treat M. tuberculosis. In bioinformatics studies orthologues of this protein have been found across different microbial genera, making this an interesting target. Time-resolved X-ray crystallography will be used to examine the structural changes upon substrate binding and during the catalytic process.
Fragment-Based Drug Discovery (FBDD) has emerged as a pivotal approach in drug development, offering notable success with the approval of six drugs by the USFDA and over 15 candidates advancing through clinical trials. Compared to traditional high-throughput screening (HTS), FBDD is more efficient, utilizing smaller libraries of low-molecular-weight molecules that enhance chemical space sampling. This method has gained widespread adoption in both academia and industry, becoming a standard practice in major pharmaceutical companies. A crucial element of FBDD is Crystallographic Fragment Screening (CFS), where potential drug fragments are soaked into target protein crystals, followed by X-ray crystallography to elucidate binding poses. This technique, superior to other biophysical approaches, provides essential structural information to guide the chemical optimization of drug candidates. Recent advancements at synchrotron facilities, including automated sample preparation and data collection systems, have transformed crystallography into a high-throughput technique suitable for primary screening. These innovations enable the collection of hundreds of datasets per day and have led to the development of dedicated screening platforms at synchrotrons like Diamond Light Source (DLS), Swiss Light Source (SLS), and BESSY II. Aligned with these advancements, the macromolecular crystallography (MX) P11 beamline at PETRA III, operated by DESY in Hamburg, Germany, has established a fully automated protein-to-structure pipeline. This pipeline integrates cutting-edge technologies such as high-energy beams for superior resolution, automatic crystal mounting robots, and advanced data processing tools. Automated sample preparation and monitoring are facilitated by the Mosquito robot and the Rock Imager at the Sample Preparation Crystallography (SPC) lab, while the Echo acoustic liquid handler and the Shifter robot automate soaking and fishing steps. The P11 pipeline significantly enhances the efficiency of FBDD campaigns, enabling rapid and effective drug discovery processes. This system has been rigorously tested with diverse protein targets, including WD Repeat Domain 5 (WDR5) and the VPS29-COMMD1-BAT3 (VCB) complex, using the Universal F2X fragments library developed by BESSY II. Most FBDD campaigns at P11 are completed within a week, from crystal acquisition to data analysis, although timelines may vary depending on target complexity and fragment library size. In conclusion, the automated pipeline at PETRA III's P11 beamline exemplifies the integration of advanced crystallographic techniques and automation in FBDD, offering a powerful platform for drug discovery and development. This facility continues to contribute to the growing success of FBDD in identifying and optimizing new drug candidates.
Facilities on campus will present themselves, what they have to offer, how to approach them/make bookings etc.
A broad range of light microscopy technologies are available within the Technology Platform Light Microscopy (TPLM) of UHH and the Advanced Light and Fluorescence Microscopy (ALFM) Facility at CSSB Hamburg. Light microscopy has its merits when proteins and their function need to be investigated within intact cells. I will present an overview of the microscopes and services offered by TPLM and ALFM that can prevent Waterloo moments in structural biology research projects and instead turn you into a Dancing Queen.
Informative talks about different funding opportunities for Hamburg structural biologists
Feedback from the audience on the organisation and execution of the meeting. Discussion about the future of the meeting (yearly?), joint seminars etc.