Biology subjects

Brunner, M.

Publications and source records attributed to Brunner, M..

25 records · Page 2Linked to original sources

bioRxiv2020

Characterising the epidemic spread of Influenza A/H3N2 within a city through phylogenetics

Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, its local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. We find trends in transmission dynamics correlated positively with trends in temperature, but not relative humidity nor school holidays. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the elderly were to a large extent infected within their own transmission network, while school children likely drove the spread within the remaining transmission network. These patterns will be valuable to plan interventions combating the spread of respiratory diseases within cities given that similar patterns are observed for other influenza seasons and cities. Author summaryAs shown with the current SARS-CoV-2 pandemic, respiratory diseases can quickly spread around the globe. While it can be hugely important to understand how diseases spread around the globe, local spread is most often the main driver of novel infections of respiratory diseases such as SARS-CoV-2 or influenza. We here use genetic sequence data alongside patient information to better understand what the drives the local spread of influenza by looking at the 2016/2017 influenza season in Basel, Switzerland as an example. The genetic sequence data allows us to reconstruct the how the transmission dynamics changed over the course of the season, which we correlate to changes, but not humidity or school holidays. Additionally, the genetic sequence data allows us to see how individual cases are connected. Using patient information, such as age and household status our analyses suggest that the elderly mainly transmit within their own transmission network. Additionally, they suggest that school aged children, but not pre-school aged children are important drivers of the local spread of influenza.

evolutionary biology↗

bioRxiv2020

High-resolution influenza mapping of a city reveals socioeconomic determinants of transmission within and between urban quarters

With two-thirds of the global population projected to be living in urban areas by 2050, understanding the transmission patterns of viral pathogens within cities is crucial for effective prevention strategies. Here, in unprecedented spatial resolution, we analysed the socioeconomic determinants of influenza transmission in a European city. We combined geographical and epidemiological data with whole genome sequencing of influenza viruses at the scale of urban quarters and statistical blocks, the smallest geographic subdivisions within a city. We observed annually re-occurring geographic clusters of influenza incidences, mainly associated with net income, and independent of population density and living space. Vaccination against influenza was also mainly associated with household income and was linked to the likelihood of influenza-like illness within an urban quarter. Transmissions patterns within and between quarters were complex. High-resolution city-level epidemiological studies combined with social science surveys such as this will be essential for understanding seasonal and pandemic transmission chains and delivering tailored public health information and vaccination programs at the municipal level.

microbiology↗

bioRxiv2019

MXD/MIZ1 complexes activate transcription of MYC-repressed genes

MXD proteins are transcription repressors that antagonize the E-box dependent activation of genes by MYC. MYC together with MIZ1 acts also as a repressor of a subset of genes, including cell cycle inhibitor genes such as p15 and p21. A role of MXDs in regulation of MYC-repressed genes is not known. Here we report that MXDs are functionally expressed in U2OS cells and activate transcription of p15 and p21, and other MYC-repressed genes. Activation of transcription was dependent on the interaction of MXDs with MIZ1, and on an intact DNA binding domain. MIZ1-binding deficient MXD mutants interacted with MAX and were active as repressors of MYC-activated genes but failed to activate MYC-repressed genes. Mutant MXDs with reduced DNA binding affinity interacted with MAX and MIZ1 but neither repressed nor activated transcription. Overexpression of MXDs attenuated proliferation of U2OS cells predominantly via MIZ1-dependent induction of p21. Our data show that MXDs and MYC have a reciprocally antagonistic potential to regulate transcription of mutual target genes.

molecular biology↗

bioRxiv2019

Global Transcriptome Characterization and Assembly of Thermophilic Ascomycete Chaetomium thermophilum

A correct genome annotation is fundamental for research in the field of molecular and structural biology. The annotation of the reference genome Chaetomium thermophilum has been reported previously, but it is limited to open reading frames (ORFs) of genes and contains only a few noncoding transcripts. In this study, we identified and annotated by deep RNA sequencing full-length transcripts of C.thermophilum. We annotated 7044 coding genes and a large number of noncoding genes (n=4567). Astonishingly, 23% of the coding genes are alternatively spliced. We identified 679 novel coding genes and corrected the structural organization of more than 50% of the previously annotated genes. Furthermore, we substantially extended the Gene Ontology (GO) and Enzyme Commission (EC) lists, which provide comprehensive search tools for potential industrial applications and basic research. The identified novel transcripts and improved annotation will help understanding the gene regulatory landscape in C.thermophilum. The analysis pipeline developed here can be used to build transcriptome assemblies and identify coding and noncoding RNAs of other species. The R packages for gene and GO annotation database can be found under https://www.bzh.uni-heidelberg.de/brunner/Chaetomium_thermophilum.

bioinformatics↗

bioRxiv2019

An inactivation switch enables rhythms in a Neurospora clock model

An autonomous endogenous time-keeping is ubiquitous across many living organisms known as circadian clock when it has a period of about 24 hours. Interestingly, the fundamental design principle with a network of interconnected negative and positive feedback loops is conserved through evolution, although the molecular components differ. Filamentous fungus Neurospora crassa is a well established chrono-genetics model organism to investigate the underlying mechanisms. The core negative feedback loop of the clock of Neurospora is composed of the transcription activator White Collar Complex (WCC) (heterodimer of WC1 and WC2) and the inhibitory element called FFC complex which is made of FRQ (Frequency protein), FRH (Frequency interacting RNA Helicase) and CK1a (Casein kinase 1a). While exploring their temporal dynamics we investigate how limit cycle oscillations arise and how molecular switches support self-sustained rhythms. We develop a mathematical model of 10 variables with 26 parameters to understand the interactions and feedbacks among WC1 and FFC elements in nuclear and cytoplasmic compartments. We performed control and bifurcation analysis to show that our novel model produces robust oscillations with a wild-type period of 22.5 hrs. Our model reveals a switch between WC1 induced transcription and FFC assisted inactivation of WC1. Using the new model we also study possible mechanisms of glucose compensation. A fairly simple model with just 3 non-linearities helps to elucidate clock dynamics revealing a mechanism of rhythms production. The model can further be utilized to study entrainment and temperature compensation.

systems biology↗

bioRxiv2019

Integrin-dependent YAP signaling requires LAMTOR1 mediated delivery of Src to the plasma membrane

YAP signaling has emerged as an important signaling pathway involved in several normal and pathological processes. While main upstream effectors regulating its activity have been extensively studied, the interplay with other cellular processes has been far less analyzed. Here, we identified the LAMTOR complex as a new important regulator of YAP signaling. We uncovered that p18/LAMTOR1 is required for the recycling of Src on late endosomes to the cell periphery, and consequently to activate a signaling cascade that eventually controls YAP nuclear shuttling. Moreover, p18/LAMTOR1 positives late endosomes distribution is controlled by {beta}1 integrins, extracellular matrix stiffness and cell contractility. This likely relies on the targeting of microtubules to {beta}1 positive focal adhesion via ILK. Altogether our findings identify the late endosomal recycling pathway as a major regulator of YAP.

cell biology↗

bioRxiv2018

Use of a corneal impression membrane for the detection of Herpes Simplex Virus type-1

PurposeTo investigate the use of a corneal impression membrane (CIM) for the detection of Herpes Simplex Virus type 1 (HSV-1) in suspected Herpes Simplex Keratitis (HSK).\n\nMaterials and MethodsIn the laboratory study, swabs and CIMs made from polytetrafluoroethylene were spiked with different concentrations of HSV-1. DNA was extracted and real time PCR undertaken using 2 sets of primers. In the clinical study consecutive patients presenting with suspected HSK were included. For each patient, samples were collected from corneal lesions with a swab and a CIM in random order. Clinical details were collected using a standardised clinical form and patients were categorized into probable, presumed and possible HSK.\n\nResultsThere was no difference in the performance of both primer sets for all HSV-1 dilutions (p=0.83) or between a CIM and a swab (p=0.18). 110 patients were included. Seventy-three patients (66.4%) had probable, 20 patients (18.2%) presumed, and 17 patients (15.5%) possible HSV-1 keratitis. The HSV-1 detection rate was significantly higher using a CIM (40/110, 36.4%) than a swab (28/110, 25.5%) (p=0.004). In the probable HSV keratitis group, the detection rate using a CIM was 43.8% compared to 27.4% for a swab (p=0.004). The Cp values obtained for the conjunctival swabs were higher than those obtained for the CIMs (p<0.001).\n\nConclusionsIn suspected HSK, a CIM is a useful alternative to a swab and more likely to detect the presence of HSV-1.

microbiology↗