SALVE Inaguration ceremony 11-14 December
3rd SALVE symposium
December 12 to 14, 2017 - The 3rd Sub-Angstrom Low-Voltage Electron Microscopy (SALVE) Symposium brings together distinguished scientists from all over the world to discuss low-voltage instrumentation and its applications. A particular focus will be given to the manufacturing of low-dimensional materials and the assessment of their properties by theoretical calculations. Various TEM techniques will be discussed - (S)TEM imaging, in-situ TEM, electron holography, cryo-TEM and spectroscopy. Finally, challenges and prospects of low-voltage imaging of biologically relevant objects will be addressed.
Place: Room 2619, O23
Time: from 14h45
CRC Seminar Prof. Ulrich Flögel 4th of December 2017
Place: Room 227, N24
CRC Seminar Prof. Halvard Bönig 20th of November 2017
Novel insights about the role of CXCR4 in immature hematopoiesis, gleaned in the process of developing a novel clinical CXCR4 antagonist using PEM technology
Place: Room 227, N24
CRC Seminar Prof. Martin Plenio 13th of November 2017
Hyperpolarized peptide-coated nanodiamonds for magnetic resonance imagingPlace:
CRC Seminar W.E Moerner 6th of November 2017 (Nobel laureate)
The Promise and Challenges of 3D Super-Resolution Microscopy, Single-Molecule Tracking in Cells, and Trapping of Biomolecules in Solution
It is worth remembering that the first optical detection of single molecules arose out of an industrial research lab in the late 1980’s, while exploring the fundamentals of molecular frequency domain optical storage at low temperatures. This work led to the observations of blinking and optical switching, key concepts that provide the foundations of super-resolution imaging with single molecules. Super-resolution microscopy has opened up a new frontier in which biological structures and behavior can be observed in fixed and live cells with resolutions down to 20-40 nm and below, and many examples abound. Current methods development research addresses ways to image in thick cells and to extract more information from each single molecule such as 3D position and orientation, as well as to assure not only precision, but also accuracy. Further, new labels are needed which provide more photons before photobleaching. At the same time, it is worth noting that in spite of all the current focus on super-resolution, even in the “conventional” low concentration, single-molecule tracking regime where the motions of individual biomolecules are recorded rather than the shapes of extended structures, much can be learned about dynamic biological processes when ensemble averaging is removed. Beyond tracking, trapping of single molecules in solution for extended measurement of multiple variables is a powerful way to examine photodynamics of photosynthetic antenna proteins and other biomolecules.
Place: Multimedia room , N27
CRC Seminar Prof. Christian Buske 23rd of October 2017
Understanding how Monocytes and CD34+ Progenitors Promote Persistence of Human Cytomegalovirus
Place: H10, M24
CRC Seminar Prof. Thomas Schrader 16th of October 2017
Supramolecular tools to modulate biological function
Place: Room2609/10, O23
CRC Seminar Dr. Andrew Yurochko 9th of October 2017
Characterization of endogenous peptides targeting leukemic stem cells in acute myeloid leukemia
Place: Room 2622, N23
CRC Seminar Konstantin Sparrer 25th of September 2017
The role of TRIM proteins in virus-induced autophagy
Recent studies demonstrated that members of the TRIM protein family are critical modulators of both cytokine- and autophagy-mediated antiviral defenses. While the molecular mechanisms by which TRIM proteins regulate antiviral interferon responses have been well characterized, significantly less is known about the role of TRIM proteins in autophagy in response to specific viral pathogens. Using both cDNA and RNAi screens, we systematically assessed the role of TRIM proteins in autophagy induction in response to RNA virus and DNA virus infections. While some TRIM proteins were critical for autophagy induced by specific viruses, others were essential for the autophagic response towards all tested viruses. TRIM23 emerged from the screens as a major hit. Whereas overexpression of TRIM23 induced high levels of autophagic flux, depletion of endogenous TRIM23 reduced viral- and rapamycin induced autophagy to near-basal levels, demonstrating that TRIM23 is crucial for autophagy activation in response to viral infection or rapamycin treatment. Mutational analysis showed that the autophagy-promoting activity of TRIM23 is dependent on both its N-terminal RING E3 ubiquitin ligase and C-terminal ADP-ribosylation factor (ARF) GTPase activity. Mechanistically, unconventional non-degradative K-27 linked auto-ubiquitination of the ARF domain is essential for the GTP hydrolysis activity of TRIM23, its recruitment to autophagosomes, TBK1 activation and subsequent induction of antiviral autophagy. Our study thus provides novel mechanistic insight into the role of TRIM proteins during virus-induced autophagy and identifies TRIM23 as a core component of the selective autophagy machinery.
Place: Multimediaroom, N27
CRC Seminar Jan Münch 17th of July 2017
Characterization and Optimization of EPI-X4, an endogenous antagonist of CXCR4
The CXCR4/CXCL12 signaling pair plays an essential role in cellular homeostasis and is associated with a variety of diseases such as cancer development and chronic inflammations. Furthermore, CXCR4 serves as coreceptor for HIV-1 entry. By screening a blood-derived peptide library, we identified a fragment of human serum albumin that antagonizes CXCR4. This peptide, named EPI-X4, specifically interacts with the receptor thereby blocking CXCR4 (X4)-tropic HIV-1 infection and CXCL12 signaling. EPI-X4 prevents CXCL12-mediated immune and tumor cell migration in vitro but also mobilizes stem cells and reduces inflammatory responses in vivo. Thus, EPI-X4 is an endogenous regulator of CXCR4. However, its relevance in vivo remains unclear. I will here present our project A06 that aims to clarify the (patho)-physiological processes in which EPI-X4 is involved by determining when, where, why, how and at which quantities the peptide is generated. Using humanized mice, we will also investigate whether endogenous EPI-X4 is the long-sought gatekeeper that restricts X4-tropic HIV-1 transmission. EPI-X4 is a promising candidate for clinical development because it is more specific and less toxic than Plerixafor, the only clinically approved CXCR4 antagonist. To improve key properties of EPI-X4 like anti-CXCR4 activity or the generation of ligands with biased activity, it is essential to understand how EPI-X4 works at the molecular level. I will provide an update on our recent SAR study and in silico optimization approaches based on molecular dynamics simulations, free energy calculations, computational mutagenesis and cell-based CXCR4 inhibition assays. I will also discuss studies with PIs in and outside the CRC1279 where EPI-X4 and optimized derivatives are evaluated as agents for stem cell mobilization, or the therapy of CXCR4-linked diseases such as leukemia and cancer.
Place: Multimediaroom, N27
CRC Seminar Alexander Zelikin 10th of July 2017
Medicinal polymer chemistry : From polymer design to therapeutic benefit and back
Antiviral macromolecular prodrugs, innovative bioconjugation techniques, and engineering of biocatalytic materials for biomedicine ? these areas of research are in the focus of our lab and during this presentation, we will discuss our recent findings on these avenues. I will present the development of biocatalytic implants as novel tools for site?specific drug delivery. We will also discuss the design of macromolecular prodrugs as broad?spectrum antiviral agents. Finally, I will outline our recent successes in delivery of latency reversing agents against HIV. Presentation aims to be of interest for diverse audience, specifically scientists in the fields of polymer science and engineering, medicinal chemistry, biomaterials, and virology.