A5042346979- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Mitochondrial Function and Pathology
- Autoimmune Bullous Skin Diseases
- Metabolism and Genetic Disorders
- Urticaria and Related Conditions
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- ATP Synthase and ATPases Research
- Diet and metabolism studies
- Gut microbiota and health
- Adipose Tissue and Metabolism
- Catalytic C–H Functionalization Methods
- Synthesis and biological activity
- Traditional and Medicinal Uses of Annonaceae
- Flavonoids in Medical Research
- Cutaneous lymphoproliferative disorders research
- Redox biology and oxidative stress
- Sepsis Diagnosis and Treatment
- Atherosclerosis and Cardiovascular Diseases
- Eosinophilic Esophagitis
- Genetic and Kidney Cyst Diseases
- Thermoregulation and physiological responses
- Cell Adhesion Molecules Research
- Axial and Atropisomeric Chirality Synthesis
- Neonatal and Maternal Infections
University of Lübeck
2016-2025
Institute for Integrative and Experimental Genomics
2018-2021
University of Bremen
2014
Gut microbial communities are key mediators of health and disease have the capacity to drive pathogenesis diverse complex diseases including metabolic chronic inflammatory as well aging. Host genetics is also a major determinant phenotypes, whereby two different genomes play role, nuclear (nDNA)- mitochondrial genome (mtDNA). We investigated impact mutations in mtDNA on gut microbiota using conplastic mouse strains exhibiting distinct their an identical nDNA. Each three strain tested harbors...
Abstract Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics. However, impact gene-environment interactions on phenotypic mostly remains elusive. To address this, we feed 1154 mice an autoimmunity-prone intercross line (AIL) three different diets. We find that diet substantially contributes to variability unmasks additional genetic susceptibility trait loci (QTL). By performing whole-genome sequencing AIL founder...
Abstract Octahydroindolo[2,3-a]quinolizine ring system forms the basic framework comprised of more than 2000 distinct family members natural products. Despite potential applications this privileged substructure in drug discovery, efficient, atom-economic and modular strategies for its assembly, is underdeveloped. Here we show a one-step build/couple/pair strategy that uniquely allows access to diverse octahydroindolo[2,3-a]quinolizine scaffolds with three contiguous chiral centers broad...
We previously demonstrated that mice carrying natural mtDNA variants of the FVB/NJ strain (m.7778 G>T in mt-Atp8 gene mitochondrial complex V), namely C57BL/6 J-mt
Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e., the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum diseases but also physiological processes, including endurance exercise performance athletes. However, phenotypic consequences limited levels naturally arising heteroplasmy have not been experimentally studied date. We hence generated conplastic mouse strain carrying genome an AKR/J (B6-mtAKR) C57BL/6 J nuclear genomic...
Several genetic variants in the mitochondrial genome (mtDNA), including ancient polymorphisms, are associated with chronic inflammatory conditions, but investigating functional consequences of such mtDNA polymorphisms humans is challenging due to influence many other both and nuclear (nDNA). Here, using conplastic mouse strain B6-mtFVB, we show that mice, a maternally inherited natural mutation (m.7778G > T) mitochondrially encoded gene ATP synthase 8 (mt-Atp8) complex V impacts on...
Introduction Inflammatory epidermolysis bullosa acquisita (EBA) is characterized by a neutrophilic response to anti-type VII collagen (COL7) antibodies resulting in the development of skin inflammation and blistering. The antibody transfer model EBA closely mirrors this phenotype. Methods To better understand changes induced neutrophils upon recruitment from peripheral blood into lesional EBA, we performed single-cell RNA-sequencing whole dissociate capture minimally perturbed characterize...
In this study, we provide experimental evidence that a maternally inherited polymorphism in the mitochondrial cytochrome b gene (mt-Cytb; m.15124A>G, Ile-Val) complex III resulted middle-aged obesity and higher susceptibility to diet-induced obesity, as well age-related inflammatory disease, e.g., ulcerative dermatitis, mice. As consequence of variation, observed alterations body composition, metabolism functions, i.e., increased oxygen consumption rate levels reactive species, commensal...
Nitrogen and oxygen medium rings, in particular nine-membered epitomize a unique area of chemical space that occurs many natural products biologically appealing compounds. The scarcity 8- to 12-membered rings among clinically approved drugs is indicative the difficulties associated with their synthesis, principally owing unfavorable entropy transannular strain. We report here scandium triflate-catalyzed reaction allows for modular access diverse collection ring heterocycles one-pot cascade...
We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mtBPL mice m.11902T>C and B6-mtALR m.4738C>A. exhibited a longer lifespan lower metabolic disease susceptibility despite mild functional differences steady-state. As natural polymorphisms DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated microbiota composition these strains. In line...
Mitochondrial complex I-the largest enzyme of the mitochondrial oxidative phosphorylation machinery-has been proposed to contribute a variety age-related pathological alterations as well longevity. The complex-consisting proteins are encoded by both nuclear (nDNA) and DNA (mtDNA). While some association studies mtDNA I genes lifespan in humans have reported, experimental evidence functional consequence such variants is limited using invertebrate models. Here, we present that homoplasmic...
(1) Background: Today, the discovery of novel anticancer agents with multitarget effects and high safety margins represents a challenge. Drug efforts indicated that benzopyrane scaffolds possess wide range pharmacological activities. This spurs on building skeletally diverse library benzopyranes to identify an lead drug candidate. Here, we aim characterize effect derivative, aiming develop promising clinical (2) Methods: The SIMR1281 against panel cancer cell lines was tested. In vitro...
Background: Neonatal sepsis is a global health problem that mainly affects low- and middle-income countries. We have previously shown early neonatal mortality high at the Ho Teaching Hospital (HTH) of Ghana. sought to determine prevalence sepsis, sepsis-related mortality, bacterial species patterns in young infant this hospital. Methods: A hospital-based study was conducted hospital's intensive care unit (NICU) from March June 2018. Blood samples 96 babies clinically diagnosed with or risk...
Summary Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e. the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum diseases but also physiological processes, including endurance exercise performance athletes. However, phenotypic consequences limited levels naturally-arising heteroplasmy have not been experimentally studied date. We hence generated conplastic mouse strain carrying genome AKR/J (B6-mt AKR ) together with C57BL/6J nuclear...