Publications by authors named "Olga Mielczarek"

Gene editing technologies hold promise for enabling the next generation of adoptive cellular therapies. In conventional gene editing platforms that rely on nuclease activity, such as clustered regularly interspaced short palindromic repeats CRISPR-associated protein 9 (CRISPR-Cas9), allow efficient introduction of genetic modifications; however, these modifications occur via the generation of DNA double-strand breaks (DSBs) and can lead to unwanted genomic alterations and genotoxicity. Here, we apply a novel modular RNA aptamer-mediated Pin-point base editing platform to simultaneously introduce multiple gene knockouts and site-specific integration of a transgene in human primary T cells.

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Article Synopsis
  • The study focuses on the structural changes in immunoglobulin heavy-chain (Igh) loci that create diverse antibody repertoires, revealing the complexity of chromosomal interactions involved.
  • Using a technique called tiled Capture Hi-C, researchers mapped chromatin interactions in the Igh locus of progenitor B cells, showing how the locus forms subdomains and flexible loops for gene recombination.
  • They found that the unique structures of the Igh locus, along with interactions between different immunoglobulin loci and developmental factors, suggest a coordinated network that influences B cell development and antibody diversity.
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Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterized by enthesitis of the spine and sacroiliac joints. Genome-wide association studies (GWASs) have revealed more than 100 genetic associations whose functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls.

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The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) disease (COVID-19) pandemic has caused millions of deaths worldwide. Genome-wide association studies identified the 3p21.31 region as conferring a twofold increased risk of respiratory failure.

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Driven by the necessity to survive environmental pathogens, the human immune system has evolved exceptional diversity and plasticity, to which several factors contribute including inheritable structural polymorphism of the underlying genes. Characterizing this variation is challenging due to the complexity of these loci, which contain extensive regions of paralogy, segmental duplication and high copy-number repeats, but recent progress in long-read sequencing and optical mapping techniques suggests this problem may now be tractable. Here we assess this by using long-read sequencing platforms from PacBio and Oxford Nanopore, supplemented with short-read sequencing and Bionano optical mapping, to sequence DNA extracted from CD14+ monocytes and peripheral blood mononuclear cells from a single European individual identified as HV31.

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Article Synopsis
  • The text discusses how the adaptive immune system creates a diverse range of antigen receptors (AgRs) through a process called V(D)J recombination, utilizing a limited number of genes while overcoming spatial and temporal challenges.
  • Advances in technology have improved our understanding of the immunoglobulin heavy chain (Igh) locus structure and its regulatory elements, particularly focusing on recent sequencing methods and imaging studies that reveal how Igh undergoes dynamic changes during recombination.
  • Key factors that regulate the Igh locus, such as transcription factors and structural proteins, are examined, along with exciting new findings related to the mechanisms of recombination, including Rag recombinase activity and an emerging phase separation model for compartment
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Circadian clocks drive rhythmic physiology and metabolism to optimize plant growth and performance under daily environmental fluctuations caused by the rotation of the planet. Photosynthesis is a key metabolic process that must be appropriately timed to the light-dark cycle. The circadian clock contributes to the regulation of photosynthesis, and in turn the daily accumulation of sugars from photosynthesis also feeds back to regulate the circadian oscillator.

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Circadian clocks provide a competitive advantage in an environment that is heavily influenced by the rotation of the Earth, by driving daily rhythms in behaviour, physiology and metabolism in bacteria, fungi, plants and animals. Circadian clocks comprise transcription-translation feedback loops, which are entrained by environmental signals such as light and temperature to adjust the phase of rhythms to match the local environment. The production of sugars by photosynthesis is a key metabolic output of the circadian clock in plants.

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