publications of the department of RNA biology of bacterial infections([HIRI] RABI)
http://hdl.handle.net/10033/620969
2024-03-28T13:31:24Z
2024-03-28T13:31:24Z
Merging bioresponsive release of insulin-like growth factor I with 3D printable thermogelling hydrogels
Beudert, Matthias
Hahn, Lukas
Horn, Anselm H.C.
Hauptstein, Niklas
Sticht, Heinrich
Meinel, Lorenz
Luxenhofer, Robert
Gutmann, Marcus
Lühmann, Tessa
http://hdl.handle.net/10033/623192
2022-06-11T02:16:45Z
2022-07-01T00:00:00Z
Merging bioresponsive release of insulin-like growth factor I with 3D printable thermogelling hydrogels
Beudert, Matthias; Hahn, Lukas; Horn, Anselm H.C.; Hauptstein, Niklas; Sticht, Heinrich; Meinel, Lorenz; Luxenhofer, Robert; Gutmann, Marcus; Lühmann, Tessa
3D printing of biomaterials enables spatial control of drug incorporation during automated manufacturing. This study links bioresponsive release of the anabolic biologic, insulin-like growth factor-I (IGF-I) in response to matrix metalloproteinases (MMP) to 3D printing using the block copolymer of poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine) (POx-b-POzi). For that, a chemo-enzymatic synthesis was deployed, ligating IGF-I enzymatically to a protease sensitive linker (PSL), which was conjugated to a POx-b-POzi copolymer. The product was blended with the plain thermogelling POx-b-POzi hydrogel. MMP exposure of the resulting hydrogel triggered bioactive IGF-I release. The bioresponsive IGF-I containing POx-b-POzi hydrogel system was further detailed for shape control and localized incorporation of IGF-I via extrusion 3D printing for future applications in biomedicine and biofabrication. © 2022 Elsevier B.V.
2022-07-01T00:00:00Z
Global RNA interactome of Salmonella discovers a 5' UTR sponge for the MicF small RNA that connects membrane permeability to transport capacity.
Matera, Gianluca
Altuvia, Yael
Gerovac, Milan
El Mouali, Youssef
Margalit, Hanah
Vogel, Jörg
http://hdl.handle.net/10033/623159
2022-02-08T02:25:21Z
2022-01-20T00:00:00Z
Global RNA interactome of Salmonella discovers a 5' UTR sponge for the MicF small RNA that connects membrane permeability to transport capacity.
Matera, Gianluca; Altuvia, Yael; Gerovac, Milan; El Mouali, Youssef; Margalit, Hanah; Vogel, Jörg
The envelope of Gram-negative bacteria is a vital barrier that must balance protection and nutrient uptake. Small RNAs are crucial regulators of the envelope composition and function. Here, using RIL-seq to capture the Hfq-mediated RNA-RNA interactome in Salmonella enterica, we discover envelope-related riboregulators, including OppX. We show that OppX acts as an RNA sponge of MicF sRNA, a prototypical porin repressor. OppX originates from the 5' UTR of oppABCDF, encoding the major inner-membrane oligopeptide transporter, and sequesters MicF's seed region to derepress the synthesis of the porin OmpF. Intriguingly, OppX operates as a true sponge, storing MicF in an inactive complex without affecting its levels or stability. Conservation of the opp-OppX-MicF-ompF axis in related bacteria suggests that it serves an important mechanism, adjusting envelope porosity to specific transport capacity. These data also highlight the resource value of this Salmonella RNA interactome, which will aid in unraveling RNA-centric regulation in enteric pathogens.
2022-01-20T00:00:00Z
Concentration and composition dependent aggregation of Pluronic- and Poly-(2-oxazolin)-Efavirenz formulations in biorelevant media.
Endres, Sebastian
Karaev, Emil
Hanio, Simon
Schlauersbach, Jonas
Kraft, Christian
Rasmussen, Tim
Luxenhofer, Robert
Böttcher, Bettina
Meinel, Lorenz
Pöppler, Ann-Christin
http://hdl.handle.net/10033/623100
2021-11-20T03:17:56Z
2021-08-10T00:00:00Z
Concentration and composition dependent aggregation of Pluronic- and Poly-(2-oxazolin)-Efavirenz formulations in biorelevant media.
Endres, Sebastian; Karaev, Emil; Hanio, Simon; Schlauersbach, Jonas; Kraft, Christian; Rasmussen, Tim; Luxenhofer, Robert; Böttcher, Bettina; Meinel, Lorenz; Pöppler, Ann-Christin
Many drugs and drug candidates are poorly water-soluble. Intestinal fluids play an important role in their solubilization. However, the interactions of intestinal fluids with polymer excipients, drugs and their formulations are not fully understood. Here, diffusion ordered spectroscopy (DOSY) and nuclear Overhauser effect spectroscopy (NOESY), complemented by cryo-TEM were employed to address this. Efavirenz (EFV) as model drug, the triblock copolymers Pluronic® F-127 (PF127) and poly(2-oxazoline) based pMeOx-b-pPrOzi-b-pMeOx (pOx/pOzi) and their respective formulations were studied in simulated fed-state intestinal fluid (FeSSIF). For the individual polymers, the bile interfering nature of PF127 was confirmed and pure pOx/pOzi was newly classified as non-interfering. A different and more complex behaviour was however observed if EFV was involved. PF127/EFV formulations in FeSSIF showed concentration dependent aggregation with separate colloids at low formulation concentrations, a merging of individual particles at the solubility limit of EFV in FeSSIF and joint aggregates above this concentration. In the case of pOx/pOzi/EFV formulations, coincident diffusion coefficients for pOx/pOzi, lipids and EFV indicate joint aggregates across the studied concentration range. This demonstrates that separate evaluation of polymers and drugs in biorelevant media is not sufficient and their mixtures need to be studied to learn about concentration and composition dependent behaviour.
2021-08-10T00:00:00Z
A Review of the Multipronged Attack of Herpes Simplex Virus 1 on the Host Transcriptional Machinery.
Hennig, Thomas
Djakovic, Lara
Dölken, Lars
Whisnant, Adam W
http://hdl.handle.net/10033/623083
2021-10-29T01:58:42Z
2021-09-14T00:00:00Z
A Review of the Multipronged Attack of Herpes Simplex Virus 1 on the Host Transcriptional Machinery.
Hennig, Thomas; Djakovic, Lara; Dölken, Lars; Whisnant, Adam W
Autophagy is an evolutionary conserved catabolic pathway that ensures the degradation of intracellular components. The autophagic pathway is regulated by autophagy-related (Atg) proteins that govern formation of double-membraned vesicles called autophagosomes. Autophagy deficiency in regulatory T (Treg) cells leads to increased apoptosis of these cells and to the development of autoimmune disorders, predominantly characterized by intestinal inflammation. Recently, RORγt-expressing Treg cells have been identified as key regulators of gut homeostasis, preventing intestinal immunopathology. To study the role of autophagy in RORγt+ Foxp3+ Treg cells, we generated mice lacking the essential component of the core autophagy machinery Atg5 in Foxp3+ cells. Atg5 deficiency in Treg cells led to a predominant intestinal inflammation. While Atg5-deficient Treg cells were reduced in peripheral lymphoid organs, the intestinal RORγt+ Foxp3+ subpopulation of Treg cells was most severely affected. Our data indicated that autophagy is essential to maintain the intestinal RORγt+ Foxp3+ Treg population, thereby protecting the mice from gut inflammatory disorders.
2021-09-14T00:00:00Z