A5060362472- Chronic Lymphocytic Leukemia Research
- Antibiotic Resistance in Bacteria
- CRISPR and Genetic Engineering
- Bacterial Genetics and Biotechnology
- Bacterial Identification and Susceptibility Testing
- Bacteriophages and microbial interactions
- Antimicrobial Resistance in Staphylococcus
- Acute Lymphoblastic Leukemia research
- Tuberculosis Research and Epidemiology
- Gut microbiota and health
- Pharmaceutical and Antibiotic Environmental Impacts
- Single-cell and spatial transcriptomics
- Protein Tyrosine Phosphatases
- Mycobacterium research and diagnosis
- Diagnosis and treatment of tuberculosis
- Angiogenesis and VEGF in Cancer
- Genetic factors in colorectal cancer
- Evolution and Genetic Dynamics
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Axon Guidance and Neuronal Signaling
- RNA and protein synthesis mechanisms
- Colorectal Cancer Treatments and Studies
- melanin and skin pigmentation
- Immunodeficiency and Autoimmune Disorders
Uppsala University
2015-2025
Science for Life Laboratory
2016-2025
Swedish University of Agricultural Sciences
2008
PMEL is an amyloidogenic protein that appears to be exclusively expressed in pigment cells and forms intralumenal fibrils within early stage melanosomes upon which eumelanins deposit later stages. well conserved among vertebrates, allelic variants several species are associated with reduced levels of eumelanin epidermal tissues. However, most these cases it not clear whether the reflect gain-of-function or loss-of-function, no complete loss-of-function has been reported a mammal. Here, we...
NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within pathway a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, negative regulator normal B cells. Strikingly, 13 these cases carried an identical 4-bp frameshift deletion, resulting truncated...
Abstract Homologous recombination is essential for the accurate repair of double-stranded DNA breaks (DSBs) 1 . Initially, RecBCD complex 2 resects ends DSB into 3′ single-stranded on which a RecA filament assembles 3 Next, locates homologous template sister chromosome 4 Here we directly visualize DSBs in single cells, using high-throughput microfluidics and fluorescence microscopy. We find that, Escherichia coli , between segregated loci completed 15 ± 5 min (mean s.d.) with minimal fitness...
Abstract Antimicrobial resistance is an increasing problem on a global scale. Rapid antibiotic susceptibility testing (AST) urgently needed in the clinic to enable personalized prescriptions high-resistance environments and limit use of broad-spectrum drugs. Current rapid phenotypic AST methods do not include species identification (ID), leaving time-consuming plating or culturing as only available option when ID make sensitivity call. Here we describe method perform at single-cell level...
The rise of antibiotic-resistant bacterial infections poses a global threat. Antibiotic resistance development is generally studied in batch cultures which conceals the heterogeneity cellular responses. Using single-cell imaging, we growth response Escherichia coli to sub-inhibitory and inhibitory concentrations nine antibiotics. We found that increases more than what expected from rate reduction for three out antibiotics tested. For two (rifampicin nitrofurantoin), sub-populations were able...
Method17 October 2017Open Access In situ genotyping of a pooled strain library after characterizing complex phenotypes Michael J Lawson Department Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden Search more papers by this author Daniel Camsund Jimmy Larsson Özden Baltekin David Fange Johan Elf Corresponding Author [email protected] orcid.org/0000-0001-5522-1810 Information Lawson1,‡, Camsund1,‡, Larsson1, Baltekin1, Fange1 *,1 1Department ‡These...
Many bacterial species and antibiotic classes exhibit heteroresistance, a phenomenon in which susceptible isolate harbors resistant subpopulation that can grow the presence of an cause treatment failure. The phenotype is often unstable without selection it reverts back to susceptibility. Here we studied dynamics by these subpopulations are enriched recede their baseline frequency absence selection. An increasing understanding this instability will allow more effective diagnostics infections...
Significance To address the public health challenges caused by spread of antibiotic resistance, it is critical to enhance our understanding mechanisms action these compounds. In present study, we use superresolved single-molecule tracking techniques, investigate effect three aminoglycoside drugs on protein synthesis kinetics directly inside live bacterial cells. Our results imply that do not completely inhibit synthesis, but only make slower. Hence, bactericidal likely due a disturbed,...
The blood of a septic patient contains only few bacteria per milliliter. Recently, various techniques have been developed for extracting these from sample. Independent how are separated the cells, we want to learn them treat infection. Here, describe phenotypic Antibiotic Susceptibility Test can be executed with single bacterial cell by making averages over time instead populations, if account experimental noise and cell-to-cell variability. We use method make preliminary estimates long it...
Abstract Drug-resistant tuberculosis (DR-TB) kills ~200,000 people every year. A contributing factor is the slow turnaround time (TAT) associated with drug susceptibility diagnostics. The prevailing gold standard for phenotypic testing (pDST) takes at least two weeks. Here we show that growth-based pDST slow-growing mycobacteria can be conducted in 12 h. We use Mycobacterium variant bovis Bacillus Calmette-Guérin (BCG) and smegmatis as mycobacterial pathogen models expose them to antibiotics...
To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired to fludarabine-based chemotherapy represents a major challenge long-term disease control.We used piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, genes that confer human CLL cell line.In total, this screen identified 782 transposon integrations fludarabine-resistant pools of cells. One is known mediator DCK (deoxycytidine...
// Tatjana Pandzic 1 , Veronica Rendo Jinyeong Lim 2 Chatarina Larsson Jimmy Ivaylo Stoimenov Snehangshu Kundu Muhammad Akhtar Ali Mats Hellström Liqun He Anders M. Lindroth and Tobias Sjöblom Science for Life Laboratory, Department of Immunology, Genetics Pathology, Uppsala University, Uppsala, Sweden Cancer Biomedical Science, National Center Graduate School Policy, Goyang-si, Republic Korea Correspondence to: Sjöblom, email: tobias.sjoblom@igp.uu.se Keywords: colorectal cancer; PRDM2;...
Abstract Background: Angiogenesis is implicated in many pathological conditions. The role of the proteins involved remains largely unknown, and few vascular‐specific drug targets have been discovered. Previously, a screen for angiogenesis regulators, we identified Paladin (mouse: X99384 , human: KIAA1274 ), protein containing predicted S/T/Y phosphatase domains. Results: We present mouse knockout allele with β‐galactosidase reporter, which combination antibodies demonstrate that expressed...
We have previously shown that platelet-derived growth factor AA (PDGF-AA) stimulates the expansion of neuronal progenitors from neural stem cells, but is unable to replace fibroblast-growth 2 (FGF-2) as a cell mitogen. In present study, we compared gene expression in cells were grown presence FGF-2 and cultured with PDGF-AA or absence factor, which induces differentiation. The genetic program elicited by (156 significantly regulated genes) was not unique, an intermediate between ones...
Article28 December 2020Open Access Source DataTransparent process Paladin is a phosphoinositide phosphatase regulating endosomal VEGFR2 signalling and angiogenesis Anja Nitzsche orcid.org/0000-0003-0567-6790 Science for Life Laboratory, The Rudbeck Department of Immunology, Genetics Pathology, Uppsala University, Uppsala, SwedenThese authors contributed equally to this work Search more papers by author Riikka Pietilä Dominic T Love Chiara Testini Sweden Takeshi Ninchoji Ross O Smith Elisabet...
Abstract The DNA of bacterial cells is organized in a highly dynamic chromosome structure. To guarantee its propagation, the must replicate, segregate, and accommodate other biological processes like gene expression. Therefore, to understand causal relationship between organization function, it essential follow dynamics. Live-cell imaging fluorescent labels allows tracking specific genomic locations, but current imaging-based approaches study over cell cycle are limited their throughput....
The Ras pathway genes KRAS, BRAF, or ERBBs have somatic mutations in ~ 60% of human colorectal carcinomas. At present, it is unknown whether the remaining cases lack activating they acquired hitherto to belong pathway. To address second possibility and extend compendium genes, we used genome-wide transposon mutagenesis two cancer cell systems deprived their KRAS BRAF allele identify enabling growth low glucose, a phenotype, when targeted. Of 163 recurrently targeted different genetic...
Abstract Optical pooled screening is an important tool to study dynamic phenotypes for libraries of genetically engineered cells. However, the desired engineering often requires that barcodes used in situ genotyping are expressed from chromosome. This has not been possible bacteria. Here we describe a method with genomic Escherichia. coli . The applied measure intracellular maturation time 81 red fluorescent proteins.
Homologous recombination (HR) is essential for the accurate repair of double-stranded DNA breaks (DSBs); it begins when RecBCD2 complex resects ends DSB into 3' single-stranded (ssDNA) on which a RecA filament assembles. HR depends ability this RecA-ssDNA to locate homologous template sister chromosome. The mechanism by homology located among vast amounts heterologous not yet understood, despite long history research. Here, we directly visualize DSBs in hundreds individual cells, using...
Abstract Drug-resistant tuberculosis (TB) kills approximately 200,000 people every year. A contributing factor is the slow turnaround time associated with anti-tuberculosis drug susceptibility diagnostics. The prevailing gold standard for phenotypic testing (pDST) takes at least two weeks. In this study, we used Mycobacterium variant bovis BCG ( M. BCG) and smegmatis as models tuberculous nontuberculous pathogens. bacteria were loaded into a microfluidic chip, trapping them in microchambers,...