
Kirsten Jensen- PhD
- Senior Researcher at Imperial College London
Kirsten Jensen
- PhD
- Senior Researcher at Imperial College London
About
51
Publications
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Introduction
Current institution
Publications
Publications (51)
Background
Urinary tract infections (UTIs) are a leading cause of hospitalization in people living with dementia, making accurate detection and prompt treatment critical in this vulnerable population.
Methods
This retrospective, longitudinal cohort study evaluated the diagnostic accuracy of self-reported symptoms and urine dipstick test results for...
Urinary Tract Infections (UTIs) are one of the most prevalent bacterial infections in older adults and a significant contributor to unplanned hospital admissions in People Living with Dementia (PLWD), with early detection being crucial due to the predicament of reporting symptoms and limited help-seeking behaviour. The most common diagnostic tool i...
While recent advances in cryo-EM, coupled with single particle analysis, have the potential to allow structure determination in a near-native state from vanishingly few individual particles, this vision has yet to be realised in practise. Requirements for particle numbers that currently far exceed the theoretical lower limits, challenges with the p...
While recent advances in cryogenic electron microscopy coupled with single particle analysis have the potential to allow structure determination in a near-native state from vanishingly few individual particles, this vision has yet to be realised in practise. Requirements for particle numbers that currently far exceed the theoretical lower limits, c...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The SARS-CoV-2 pandemic has shown how a rapid rise in demand for patient and community sample testing can quickly overwhelm testing capability globally. With most diagnostic infrastructure dependent on specialized instruments, their exclusive reagent supplies quickly become bottlenecks, creating an urgent need for approaches to boost testing capaci...
The SARS-CoV-2 pandemic has shown how the rapid rise in demand for patient and community sample testing, required for tracing and containing a highly infectious disease, has quickly overwhelmed testing capability globally. With most diagnostic infrastructure dependent on specialised instruments, their exclusive reagent supplies quickly become bottl...
The field of mammalian synthetic biology is expanding quickly, and technologies for engineering large synthetic gene circuits are increasingly accessible. However, for mammalian cell engineering, traditional tissue culture methods are slow and cumbersome, and are not suited for high-throughput characterization measurements. Here we have utilized ma...
Significance
Nonmodel bacteria have essential roles to play in the future development of biotechnology by providing new sources of biocatalysts, antibiotics, hosts for bioproduction, and engineered “living therapies.” The characterization of such hosts can be challenging, as many are not tractable to standard molecular biology techniques. This pape...
Synthetic biology designed cell-free biosensors are a promising new tool for the detection of clinically relevant biomarkers in infectious diseases. Here, we report that a modular DNA-encoded biosensor in cell-free protein expression systems can be used to measure a bacterial biomarker of Pseudomonas aeruginosa infection from human sputum samples....
Significance
Bacterial cellulose is a remarkable material that is malleable, biocompatible, and over 10-times stronger than plant-based cellulose. It is currently used to create materials for tissue engineering, medicine, defense, electronics, acoustics, and fabrics. We describe here a bacterial strain that is readily amenable to genetic engineerin...
Parasitic diseases affect millions of people worldwide, causing debilitating illnesses and death. Rapid and cost-effective approaches to detect parasites are needed, especially in resource-limited settings. A common signature of parasitic diseases is the release of specific proteases by the parasites at multiple stages during their life cycles. To...
The nuclei of higher eukaryotic cells display compartmentalization and certain nuclear compartments have been shown to follow a degree of spatial organization. To date, the study of nuclear organization has often involved simple quantitative procedures that struggle with both the irregularity of the nuclear boundary and the problem of handling repl...
Biopolymers, such as poly-3-hydroxybutyrate (P(3HB)) are produced as a carbon store in an array of organisms and exhibit characteristics which are similar to oil-derived plastics, yet have the added advantages of biodegradability and biocompatibility. Despite these advantages , P(3HB) production is currently more expensive than the production of oi...
Biopolymers, such as poly-3-hydroxy-butyrate (P(3HB)) are produced as a carbon store in an array of organisms and exhibit characteristics which are similar to oil-derived plastics, yet have the added advantages of biodegradability and biocompatibility. Despite these advantages, P(3HB) production is currently more expensive than the production of oi...
A bottleneck in our capacity to rationally and predictably engineer biological systems is the limited number of well-characterized
genetic elements from which to build. Current characterization methods are tied to measurements in living systems, the transformation
and culturing of which are inherently time-consuming. To address this, we have valida...
Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cle...
Tripartite motif (TRIM) proteins are defined by their possession of a RING, B-box and predicted coiled coil (RBCC) domain. The coiled-coil region facilitates the oligomerisation of TRIMs and contributes to the formation of high molecular weight complexes that show interesting subcellular compartmentalisations and structures. TRIM protein compartmen...
We have previously demonstrated that the two Exonuclease III (Xth) family members present within the obligate human pathogen
Neisseria meningitidis, NApe and NExo, are important for survival under conditions of oxidative stress. Of these, only NApe possesses AP endonuclease
activity, while the primary function of NExo remained unclear. We now revea...
In the past 20 years cell biologists have studied the cell nucleus extensively, aided by advances in cell imaging technology
and microscopy. Consequently, the volume of image data of the cell nucleus – and the compartments it contains – is growing
rapidly. The spatial organisation of these nuclear compartments is thought to be fundamentally associa...
Considerable advances in microscopy, biophysics, and cell biology have provided a wealth of imaging data describing the functional organization of the cell nucleus. Until recently, cell nuclear architecture has largely been assessed by subjective visual inspection of fluorescently labeled components imaged by the optical microscope. This approach i...
Promyelocytic leukaemia nuclear bodies (PML NBs) are found within the nucleus of mammalian cells, and are formed from the constituent proteins PML and Sp100. Numbering between 10 and 30 per cell, they are an obvious feature of the nuclear landscape, yet their functions have still to be unambiguously defined. In the mammalian nucleus, compartmentali...
Oxidative stress is a principal cause of DNA damage, and mechanisms to repair this damage are among the most highly conserved of biological processes. Oxidative stress is also used by phagocytes to attack bacterial pathogens in defence of the host. We have identified and characterised two apurinic/apyrimidinic (AP) endonuclease paralogues in the hu...
Caspase-8-binding protein FLICE-associated huge protein (FLASH) has been proposed to regulate death receptor CD95-induced apoptosis through facilitating caspase-8 activation at the death-inducing signaling complex. Here, we found that FLASH interacts with the PML nuclear body component Sp100 and predominantly resides in the nucleus and nuclear bodi...
PLU-1 is a large (1544 amino acids) nuclear protein that is highly expressed in breast cancers and is proposed to function as a regulator of gene expression. A yeast two-hybrid screen using PLU-1 as bait has identified two unrelated PLU-1 interacting proteins, namely brain factor-1 (BF-1) and paired box 9 (PAX9), both of which are developmental tra...
PML is a component of a multiprotein complex, termed nuclear bodies, and the PML protein was originally discovered in patients suffering from acute promyelocytic leukaemia (APL). APL is associated with a reciprocal chromosomal translocation of chromosomes 15 and 17, which results in a fusion protein comprising PML and the retinoic acid receptor alp...
Covalent modification of the promyelocytic leukaemia protein (PML) by SUMO-1 is a prerequisite for the assembly of nuclear bodies (NBs), subnuclear structures disrupted in various human diseases and linked to transcriptional and growth control. Here we demonstrate that p53 is recruited into NBs by a specific PML isoform (PML3) or by coexpression of...
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, caused by mutations in the autoimmune regulator (AIRE) gene, is an autosomal recessive autoimmune disease characterized by the breakdown of tolerance to organ-specific antigens. The 545 amino acid protein encoded by AIRE contains several structural motifs suggestive of a transcriptiona...
Several murine IgM monoclonal antibodies (mAbs) promoting remyelination in mice were shown to be germline gene-encoded natural autoantibodies that react with oligodendrocytes and intracellular antigens. Here, we show that human oligodendrocyte-reactive IgM mAb DS1F8 derived from a patient with multiple sclerosis targets microtubule-like structures...
Fusion proteins involving the retinoic acid receptor α (RARα) and PML or PLZF nuclear protein are the genetic markers of acute
promyelocytic leukemia (APL). APLs with PML-RARα or PLZF-RARα fusion protein differ only in their response to retinoic acid
(RA) treatment: the t(15;17) (PML-RARα-positive) APL blasts are sensitive to RA in vitro, and patie...
The Sp100 and promyelocytic leukemia proteins (PML) are constituents of nuclear domains, known as nuclear dots (NDs) or PML bodies, and are both covalently modified by the small ubiquitin-related protein SUMO-1. NDs play a role in autoimmunity, virus infections, and in the etiology of acute promyelocytic leukemia. To date, little is known about the...
Sp100 and PML are interferon-inducible proteins associated with a new class of nuclear domains (known as nuclear dots or PML bodies) which play a role in tumorigenesis, virus infections, and autoimmunity. While PML is extensively alternatively spliced, only two splice variants are known for Sp100. Here we describe the identification and characteriz...
Nuclear dots (NDs), alternatively designated nuclear bodies (NBs), PML oncogenic domains (PODs), nuclear domain 10 (ND10) or Kr-bodies, became a major topic for researchers in many fields only recently. Originally described as an autoantigenic target in patients with primary biliary cirrhosis, they are now also known to play a role in development o...
PML and Sp100 proteins are associated with nuclear domains, known as nuclear dots (NDs). They were discovered in the context of leukemic transformation and as an autoantigen in primary biliary cirrhosis, respectively. Both proteins are expressed in the form of many COOH-terminally spliced variants, and their expression is enhanced by interferons (I...
Nuclear dots containing PML and Sp100 proteins (NDs) play a role in the development of acute promyelocytic leukemia, are modified after infection with various viruses, and are autoimmunogenic in patients with primary biliary cirrhosis (PBC). PML and Sp100 gene expression is strongly enhanced by interferons (IFN). Based on immunostaining with a mono...
Expression of the nuclear domain-associated proteins Sp100, PML, and NDP52, is enhanced by interferons (IFNs) on the mRNA and protein level. Increase both of Sp100 and PML mRNA is due to enhanced transcription of the corresponding genes which occurs independently of cellular protein synthesis immediately upon IFN-beta addition. Here, we describe th...
Promyelocytic leukemia protein (PML) and Sp100 are transcription-regulatory proteins which colocalize in discrete nuclear dots and play a role in autoimmunity, oncogenesis and virus-host interaction. Interferons (IFNs) were shown previously to increase strongly the levels of Sp100 mRNA and protein. Here, we examined which mechanisms lead to upregul...
In human cells, three proteins are currently known to colocalize in di screte nuclear domains (designated nuclear dots): Sp100, a transcription-activating protein autoantigenic primarily in patients with primary biliary cirrhosis; PML, a tumor suppressor protein involved in development of acute promyelocytic leukemia; and NDP52, a protein of unknow...
The molecular mechanisms by which expression of a gene is down-regulated after differentiation of F9 embryonal carcinoma cells into parietal endoderm-like cells was studied by characterizing the cis- and trans-regulatory elements of the gb110 gene. This gene encodes a putative RNA helicase, and its expression is down-regulated when F9 cells are dif...
The molecular mechanisms by which expression of a gene is down-regulated after differentiation of F9 embryonal carcinoma cells into parietal endoderm-like cells was studied by characterizing the cis- and trans-regulatory elements of the gb110 gene. This gene encodes a putative RNA helicase, and its expression is down-regulated when F9 cells are dif...
The gene gb110 was originally identified by provirus integration in the Mov10 mouse strain and encodes a 110-kDa protein with potential GTP-binding activity. The gene is evolutionarily conserved, and its expression is controlled in a developmentally and cell-cycle-specific manner, suggesting that it has an important function in differentiation and...