School of the Biological SciencesNo Descriptionhttps://www.repository.cam.ac.uk/handle/1810/256062https://www.repository.cam.ac.uk/retrieve/498dec02-4f55-423d-a08c-ae7e1253cb43/2024-03-29T09:46:31Z2024-03-29T09:46:31Z54481Engineering a cyanobacteriochrome two-component system into a synthetic, light-controlled gene expression system for plantsHofmann, Robertohttps://www.repository.cam.ac.uk/handle/1810/3660632024-03-29T01:41:19Zdc.title: Engineering a cyanobacteriochrome two-component system into a synthetic, light-controlled gene expression system for plants
dc.contributor.author: Hofmann, Roberto
dc.description.abstract: Our inability to perturb the expression of genes at cellular resolution in planta has hampered our investigation of spatial and temporal dynamics. Ideally, we would like an orthogonal, genetically encoded system, that allows us to reversibly perturb the expression of genes of interest with maximal spatiotemporal resolution in a minimally invasive way.
Our lab has reengineered the CcaS/R light receptor two-component system from cyanobacterium Synechocystis sp. PCC 6803 into a plant-compatible synthetic light-controlled gene expression system called Highlighter. This system was initially deployed in transiently transformed *Nicotiana benthamiana* leaves. However, challenges remained: an incomplete mechanistic understanding of CcaS light sensing, light response spectra overlapping with plant light signalling pathways, low engineering throughput, and most importantly the inability to use the system in stably transformed plants.
Highlighter exhibits a novel blue light response not observed in wild-type CcaS/R without an obvious biochemical basis. Here I describe the use of structural modelling, spectroscopy, genetics, and functional assays to investigate how CcaS responds to blue light. I demonstrate by targeted mutagenesis, domain deletions and domain swapping, that the blue-light response is due to a not previously characterised LOV-like domain. Next, I applied this insight to engineering new versions of the protein with improved light response kinetics. Further, I describe advances in engineering Highlighter to function in *Arabidopsis thaliana* and generate stable transgenics. I aim to target GA20OX1, a gibberellin (GA) synthesis gene with the aim of modifying GA patterns visualised by the FRET-based biosensor nlsGPS1 developed by our group. To speed up *in planta* testing of new Highlighter variants, I developed new visual assays and worked to identify optimal light conditions for widespread deployment.
Finally, I attempted to deploy a light-controlled Cas9-based programmable transcription factor *in planta*, that has recently been developed for use in mammalian cells. I demonstrate the ability of the system to induce gene expression in planta in the first step to developing the system into a viable optogenetic system for use in plants.
Studies on voltage-gated sodium channel β3 subunit structure and cancer-related functions using single-chain variable fragment antibodies and bioinformaticsLiu, Hengruihttps://www.repository.cam.ac.uk/handle/1810/3662822024-03-29T01:48:34Zdc.title: Studies on voltage-gated sodium channel β3 subunit structure and cancer-related functions using single-chain variable fragment antibodies and bioinformatics
dc.contributor.author: Liu, Hengrui
dc.description.abstract: Voltage-gated sodium channels (VGSC), embedded in the plasma membrane of cells, play a pivotal role in generating sodium currents and action potentials. The mammalian VGSCs consist of a large pseudo-tetrameric pore-forming α subunit, the channel protein, which associates with one or more β-subunits. In humans, nine types of VGSC Nav1 channel α subunit isoforms (Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.5, Nav1.6, Nav1.7, Nav1.8, and Nav1.9) and four types of β subunit isoforms (β1, β2, β3, and β4) (gene names: *SCN1-11A* and *SCN1-4B*) have been identified in various tissues. This thesis describes the use of single-chain variable fragment (scFv) antibodies to study the binding site of the β3 subunit on the pain-sensing channel, Nav1.7, and investigate the role of the VGSC β3 subunit in cancer guided by bioinformatic analysis.
*In silico* docking was used to construct a binding model between the Nav1.7 α subunit and β3 subunit, and molecular dynamic simulations were employed to assess the binding stability of this model. These computational structural analyses provide an *in silico* model that was validated in subsequent scFv mapping experiments. Using scFvs that specifically recognized distinct regions of Nav1.7, the binding site of the β3 subunit on the Nav1.7 α subunit was identified. The results substantiate that the β3 subunit binds to the Nav1.7 α subunit in a manner akin to the β1 subunit. This study offers a valuable strategy for studying the extracellular domain of plasma membrane complexes under cellular conditions, complementing cryo-electron microscopy (cryo-EM) and X-ray crystallography approaches.
In the context of cancer research, the systematic literature review and bioinformatics analysis indicated that the expression of the VGSC β3 subunit gene (*SCN3B*) is associated with reduced glioma severity and regulated glioma immunity and migration. Subsequently, the effect of the β3 subunit on glioma cell migration was experimentally investigated. The results reveal that the β3 subunit inhibits glioma cell motility via the β3 subunit immunoglobulin (β3 Ig) domain and this function is not reliant on chemo-sensing. Instead, the β3 Ig domain governs actin-based cell protrusion, reducing network actin (lamellipodia and membrane ruffle) while augmenting bundle actin (filopodia) in glioma cells. Finally, through immunoprecipitation and mass spectrometry, several pathways underlying the regulatory function of the β3 subunit in glioma cell actin organization were identified. In conclusion, this study advances our understanding of the structure and significance of the VGSC β3 subunit in cancer biology.
Comparison of Cone-Beam Computed Tomography (CBCT), Fan-Beam Computed Tomography (FBCT), and Low-Field Magnetic Resonance Imaging (MRI) for Detection of Equine Fetlock LesionsLin, Szu-Tinghttps://www.repository.cam.ac.uk/handle/1810/3662852024-03-29T01:42:59Zdc.title: Comparison of Cone-Beam Computed Tomography (CBCT), Fan-Beam Computed Tomography (FBCT), and Low-Field Magnetic Resonance Imaging (MRI) for Detection of Equine Fetlock Lesions
dc.contributor.author: Lin, Szu-Ting
dc.description.abstract: Computed tomography (CT) and magnetic resonance imaging (MRI) have been increasingly applied to diagnosing lameness localised to the fetlock region in standing horses. A full understanding of the benefits and limitations of CT and MRI for detection of bone and soft tissue lesions is essential for the most efficient application in equine practices.
The aim of the work presented in this thesis was to compare cone-beam CT (CBCT), 64-slice fan-beam CT (FBCT), and low-field (0.27 Tesla) MRI for detection of equine fetlock lesions. The first part of the work compared imaging diagnosis and measurement of third metacarpal/metatarsal parasagittal groove and proximal phalanx (P1) sagittal groove fissure, P1 dorsoproximal osteochondral defect, palmar/plantar osteochondral disease (POD), and heterotopic mineralisation in 35 equine cadaver limbs between CBCT, FBCT, and MRI using pathological findings as a gold standard (Chapter 3, 5, 6, and 7). The second part of the work retrospectively reviewed and compared CBCT and low-field (0.27 Tesla) MR imaging findings from 24 fetlock regions of clinical patients.
The diagnosis of fetlock lesions including fissures, dorsoproximal defects, POD lesions, and heterotopic mineralisation was comparable between CBCT and FBCT, with MRI having lower sensitivity but similar specificity compared to CBCT and FBCT (Chapter 3, 5, 6, and 7). The comparison of diagnoses indicated that for detection of bone lesions and heterotopic mineralisation, CBCT and FBCT are equivalent as the diagnostic tool of choice, and although the likelihood of failing to detect the presence of lesions is higher with MRI, lesions detected on MRI are likely to be genuine. MRI also detected increased fluid accumulation related to bone lesions and soft tissue injuries associated with heterotopic mineralisation, providing unique diagnostic information not available from CBCT and FBCT.
The correlation of imaging measurements was strong between CBCT, FBCT, and MRI. The correlation with macroscopic measurements was strong in CBCT and moderate in FBCT and MRI for dorsoproximal defects, and strong in MRI and CBCT and moderate in FBCT for POD lesions (Chapter 5 and 6). The superior correlation with macroscopic measurements in CBCT compared to FBCT could indicate the benefit of superior spatial resolution of CBCT over FBCT for the particular devices used.
Retrospective review of images from clinical patients (Chapter 8) found CBCT detected altered bone attenuation and structural changes in bone lesions including POD lesion, fissure, subchondral and trabecular bone injury, P1 dorsoproximal defect, osteoarthritis, and proximal sesamoid bone injury. In contrast to morphological details provided by CBCT, MRI detected the extent of increased fluid accumulation of bone injuries, providing information relevant to pathological status of bone injuries. Detection of soft tissue injury was superior using MRI compared to CBCT, in which the differentiation of soft tissue injury from normal structure was limited by lower contrast resolution.
In conclusion, the work presented in this thesis shows that CBCT and FBCT are comparable for detection of bone lesions and heterotopic mineralisation, and MRI detects associated increased fluid accumulation and soft tissue injuries. For clinical suspicion of bone injury and heterotopic mineralisation in the fetlock region, combining CBCT or FBCT with MRI provides the most thorough evaluation of lesions. For clinical suspicion of soft tissue injury, MRI alone is sufficient for a thorough assessment of soft tissue lesions.
The spread and control of dengue and chikungunya virusesRibeiro dos Santos, Gabrielhttps://www.repository.cam.ac.uk/handle/1810/3662362024-03-27T01:46:54Zdc.title: The spread and control of dengue and chikungunya viruses
dc.contributor.author: Ribeiro dos Santos, Gabriel
dc.description.abstract: Mosquito-borne viruses such as dengue and chikungunya viruses continue to cause a substantial burden on public health globally. After decades with few tools to tackle the spread of these viruses, new interventions are becoming available. The release of Wolbachia infected mosquitoes has been shown to reduce the incidence of dengue infection. In addition, the first chikungunya vaccines will soon be licensed. However, we currently have a poor understanding of the underlying transmission dynamics of both chikungunya and dengue, and whether these dynamics differ across spatial scales. This means the potential impact of these interventions is unknown. In this thesis, I tackle critical knowledge gaps in our understanding of the transmission dynamics of dengue and chikungunya viruses across different spatial scales. I also provide estimations of the impact of new interventions, providing an avenue to their future widespread use. This thesis brings together high quality data from cohort studies, seroprevalence studies and disease surveillance systems, with sophisticated analytical approaches to answer public health relevant questions.
In the first part of my thesis, I work with data from a long running cohort study in Kamphaeng Phet province, Thailand. I used serological data from the study to explore the underlying spatial heterogeneity in dengue virus infection. I found that, in that province, dengue was transmitted consistently from one year to another with a very high rate of infection compared to other places where dengue is found. There additionally was very little spatial variation in terms of force of transmission. I showed that only around 1\% of all infections get detected by disease surveillance systems, highlighting the significant hidden burden of infection from the virus. I also explored potential drivers for transmission in these settings and found that most variation in protection against dengue was at the household level and that door screens had a significant protective effect.
In the second part of my thesis, I present the results from a large Wolbachia release project in Rio de Janeiro, Brazil, where millions of Wolbachia infected mosquitoes were released in part of the city. Underlying heterogeneity in where and when cases of dengue and chikungunya were detected had complicated the efforts to understand the impact of the release program. I developed a spatially-explicit analytical approach that characterises the underlying spatial distribution of dengue and chikungunya cases within the city and estimates the impact of the release program on incidence. I showed that despite only intermediate levels of introgression in the city, there was a significant reduction in the incidence of both viruses.
In the third section of the thesis, I estimate the global burden of chikungunya virus. I conducted a literature review to identify countries that have local transmission of chikungunya. Then, based on a series of seroprevalence studies across 26 countries, I developed serocatalytic models that estimated the history of infection in epidemic and endemic settings. I show that 113 countries have experienced chikungunya transmission. In a subset of 11 countries, the virus circulates endemically. I estimate that there are 26 million annual infections and 19,000 annual deaths globally, with the greatest burden in the WHO regions of Southeast Asia, Africa and the Americas.
The first chikungunya vaccines are currently being licensed. In the last part of the thesis, I develop a simulation-based method to critically assess the impact of different vaccination strategies for chikungunya. In particular, I assess the potential use of a vaccine stockpile in epidemic countries, as is used for other pathogens such as cholera and Ebola. For each country where chikungunya circulates, I present country-specific estimates of infections, cases and deaths averted for different vaccination campaign scenarios.
This thesis contributes to the current landscape of infectious diseases epidemiology by exploring the dynamics of transmission for dengue and chikungunya, whose burdens are one of the current biggest public health challenges. It has been written during a critical period of time where vaccines are about to be commercially available and there is an urgent need for better understanding of both pathogens dynamics. Finally, it introduced a wide range of model frameworks that can be applied and built upon to refine our knowledge about arboviral diseases. Much of my work has been conducted in close collaboration with organisations such as the Gavi Alliance, CEPI and the World Mosquito Program. This close relationship with key international bodies involved in the rollout of interventions maximises the impact of my findings.
Microglial activation and regulation by secreted chaperonesReid, Kylehttps://www.repository.cam.ac.uk/handle/1810/3662162024-03-27T01:45:45Zdc.title: Microglial activation and regulation by secreted chaperones
dc.contributor.author: Reid, Kyle
dc.description.abstract: Microglia are brain-resident macrophages and play pivotal roles in central nervous system (CNS) development, homeostasis and pathology. Calreticulin and LRPAP-1 are ubiquitously expressed protein chaperones that aid in protein folding and processing within the endoplasmic reticulum (ER). Both proteins might also be released into the extracellular space, but, if so, it is unclear whether and how they affect microglial functions when present extracellularly.
Microglia are the primary innate cells of the CNS and one of the first cell types to respond to signs of injury or inflammation. However, the mechanisms that mediate and regulate this early immune response are unclear. In this work, I show stressed microglia (inflamed, ER-stressed or apoptotic) and neurons (crushed) release calreticulin into the extracellular culture media, where it reaches nanomolar levels. Applications of nanomolar calreticulin activated microglia in culture to release pro-inflammatory cytokines and chemokines, and inhibited microglial proliferation. Nanomolar calreticulin also upregulated surface MHC-II and upregulated the expression and release of APOE, but did not change the expression of 11 other genes associated with disease-associated microglia. Microglia also migrated towards media containing extracellular calreticulin. Overall, this suggests that calreticulin can be released from stressed brain cells, and this released calreticulin can act as an alarmin to recruit and activate microglia.
Calreticulin apparently activated microglia by stimulating toll-like receptor 4 (TLR4) signalling, as nanomolar calreticulin could not activate microglia or a TLR4 reporter line when i) intracellular TLR4 signalling was blocked, ii) binding to TLR4 was blocked with function blocking antibodies, or iii) the hydrophobic binding pocket formed between TLR4 and its co-receptor MD2 was blocked. Microglial activation was also inhibited when calreticulin was pretreated with sugars, so TLR4 activation may require calreticulin’s carbohydrate-binding domain. Calreticulin partially oligomerised under the same conditions used to activate microglia, so oligomeric calreticulin might contribute to activation, but this remains unclear. Thus, calreticulin is a microglial alarmin, and activates microglia by activating TLR4.
LRP-1 and related LDL family receptors mediate many cell functions, and these receptors are inhibitable by extracellular LRPAP-1. However, it is not known whether extracellular LRPAP-1 is a physiological (or pathological) regulator of these receptors, because it is not known whether LRPAP-1 is released extracellularly in physiological conditions and concentrations sufficient to inhibit these receptors. In this work, I found that microglia activated with LPS or ER-stressed with tunicamycin released nanomolar levels of LRPAP-1. Released LRPAP-1 was detected on the surface of microglia, and anti-LRPAP-1 antibodies induced internalisation to peri-nuclear compartments, consistent with LRPAP-1 being bound to endocytic LDL family receptors. Extracellular LRPAP-1, applied at levels released by stressed microglia, did not activate microglia, nor did it prevent LPS neurotoxicity in mixed neuronal-glial cultures. However, extracellular LRPAP-1 did inhibit microglial phagocytosis of dead cells and isolated synapses.
Amyloid beta (Ab) is implicated in Alzheimer’s disease (AD), and LRPAP-1 can bind and regulate Ab uptake in a variety of cells. I show extracellular LRPAP-1 regulates microglial uptake of Ab in a serum- and concentration dependent manner. Extracellular LRPAP-1 inhibited Ab fibrillization. In mixed neuronal-glial cultures, extracellular LRPAP-1 increased Ab bound and/or internalised by neurons but reduced Ab neurotoxicity. Thus. LRPAP-1 can be released by stressed microglia to inhibit microglial phagocytosis, inhibit Ab fibrillization and inhibit Ab neurotoxicity. More generally, this work supports the novel concept that released LRPAP-1 may be an extracellular regulator of LRP-1 and related LDL family receptors and their multiple functions.
Taken together, these findings indicate that calreticulin and LRPAP-1 are secretable regulators of microglial function and are extracellular chaperones.
Research data supporting: Interrogation of RNA-protein interaction dynamics in bacterial growthVillanueva Verdejo, Enekohttps://www.repository.cam.ac.uk/handle/1810/3661572024-03-22T17:46:01Zdc.title: Research data supporting: Interrogation of RNA-protein interaction dynamics in bacterial growth
dc.contributor.author: Villanueva Verdejo, Eneko
dc.description: This record containts mass spectrometry analysis of total proteome and RBPs dynamics in E coli growth and iCLIP analysis of Yfif and HtpG.
This records contains 10 datasets, EV 1 - 10. The description for each dataset is:
Dataset EV1: MS LFQ quantification of protein abudance across E. coli growth curve. For the growth curve experiments (n = 5 for each phase), the protein abundance was quantified by label-free quantification (LFQ) and data analysis was performed using the pRoloc R package. Category refers to 'Group' label in Figure 1.
Dataset EV2: GO term annotations for proteins identified across E. coli growth curve by LFQ MS. Annotations of the 2360 proteins identified in LFQ assay and categorised into 6 groups.
Dataset EV3: MS OOPS output RNase +/- assay normalized by trypsin amount along cell growth
Dataset EV4: TMT quantification of protein abudance across E. coli growth curve. Data rendered in Figure 2 of the manuscript. Samples were takan a the lag (n=4), exponential (n=3) and stationary (n=3) phases and both the total proteome and the RBPome were subimitted for MS analyisis. Values were normalised acorss protein values for total protein and RBP separately.
Extended EV5: STREME analysis YFIF table Completed at MEMESuite interface https://meme-suite.org/meme/doc/streme.html YFIF CL peaks against the control NC peaks.
Extended EV6: Supplementary tables to phylogenetic analyses. Sheet 1: Whole Tree of Life (Binary columns indicating the presence/absence of ortholog for a given protein across the nodes of the tree of life). Sheet 2: Proteobacteria annot. Name of species and whether or not pathogenic (data represented in Fig. 4b)
Extended EV7: STREME analysis HtpG table. Completed at MEMESuite interface https://meme-suite.org/meme/doc/streme.html HtpG CL peaks against the control NC peaks.
Extended EV8: Additional information on proteomic data. Tags split to label total proteome and OOPS separately. Same tags used for each sample.
Extended EV9: Primer information for iCLIP experiment. 3′ infrared adaptor (IDT, HPLC purified DNA with 5’ phosphate), RT primers (IDT, HPLC-purified), cDNA elution oligo, PCR primers (HPLC purified)
Extended EV10: Orthologue reference table. The hierarchical orthologous groups (HOGs) for each candidate protein (i.e. experimentally uncharacterised RBPs) were retrieved from the OMA browser (https://omabrowser.org/oma/home/), these are sets of genes that are inferred to have descended from a common ancestral gene.
Fitness Landscapes, Genetic Interactions, and the Fitness of HybridsSchneemann, Hildehttps://www.repository.cam.ac.uk/handle/1810/3660912024-03-22T01:43:00Zdc.title: Fitness Landscapes, Genetic Interactions, and the Fitness of Hybrids
dc.contributor.author: Schneemann, Hilde
dc.description.abstract: When two genetically differentiated populations or species come into contact and interbreed, their hybrid offspring will contain a mosaic of the genetic variants characterising the parental lineages, re-arranged into novel combinations. The fitness of these hybrids is central to the evolution of reproductive isolation, but also plays an important role in conservation policy, and in crop and animal breeding.
Fitness landscapes are simple mathematical models that generate a rich variety of context-dependent genetic interactions, making them a useful tool for studying the ways in which these interactions affect hybrid fitness. In this thesis, I will explore a particular fitness landscape model based on Fisher’s geometric model (Fisher, 1930), which provides a flexible yet tractable framework for modelling hybridisation. Throughout, I complement the analytical and simulation results with applications to published empirical data.
First, I explore the fitness of F1 hybrids, and show how phenotypic dominance can generate a diverse range of outcomes. As the dominance effects at different loci are rarely expressed together during divergence, they are unlikely to be co-adapted. I show that, as a consequence, dominance generally reduces F1 fitness, closely resembling the effects of uniparental inheritance, Still, I predict the effects of dominance can also be beneficial, and this may help to explain transgressive hybrids that prosper in extreme environments.
Next, I present results for hybrids of any type, based on a new and more general derivation of the model. I show that predictions can be expressed in terms of two distance measures capturing the net effect and total amount of evolutionary change in terms of additive and dominance effects, as well as their interaction. Each of these terms carries information about the history of divergence, telling us about the type, direction, and subject of selection respectively.
Thinking about the long-term outcomes of hybridisation, I then investigate what we can learn from introgression line studies about coadaptation between alleles and the fixability of heterosis. Consolidating the classical theories of heterosis, I illustrate how this model generates complex genetic architectures characterised by transient overdominance.
Finally, I present an extension of the model to arbitrary ploidy which lets us investigate the effects of dosage on hybrid fitness. Applying these predictions to published data, I show how they can help to explain repeatedly observed differences in patterns of heterosis and inbreeding depression between diploids and tetraploids.
Data supporting "The socioecological benefits and consequences of oil palm cultivation in its native range: The Sustainable Oil Palm in West Africa (SOPWA) Project"Pashkevich, Michaelhttps://www.repository.cam.ac.uk/handle/1810/3660922024-03-22T01:47:01Zdc.title: Data supporting "The socioecological benefits and consequences of oil palm cultivation in its native range: The Sustainable Oil Palm in West Africa (SOPWA) Project"
dc.contributor.author: Pashkevich, Michael
dc.description: Data associated with the publication "The socioecological benefits and consequences of oil palm cultivation in its native range: The Sustainable Oil Palm in West Africa (SOPWA) Project", which has been accepted for publication in "Science of the Total Environment." There are two datasets. First, findings from a systematic review of oil palm-related research in an African context. Second, field-based findings from a large-scale, field-based project in Liberia (the Sustainable Oil Palm in West Africa, 'SOPWA', Project), focussed on differences between forest and traditionally- and industrially-managed oil palm systems. SOPWA Project data include plot-based data on soil temperature (collected using iButton dataloggers), ground vegetation cover (collected using eye estimates), and canopy cover (collected using in-field photographs and subsequent processing using Adobe Photoshop). Data were analysed in R using varying statistical methods (GLMMs, GAMMs) and visualisation techniques.
The role of polarisation in the first cell fate decision of the mouse embryoLamba, Adiyanthttps://www.repository.cam.ac.uk/handle/1810/3659822024-03-21T01:42:58Zdc.title: The role of polarisation in the first cell fate decision of the mouse embryo
dc.contributor.author: Lamba, Adiyant
dc.description.abstract: A fundamental process in embryonic development is the first cell fate decision, when cells take on distinct lineage identities for the first time. In mammals, this separates embryonic inner cell mass (ICM) from extra-embryonic trophectoderm (TE) during pre- implantation development. In the mouse, the process is classically attributed to the consequences of apical-basal polarity, which forms at the 8-cell stage: those cells which retain the apical domain after cell divisions are specified as TE, and the rest as ICM. However, more recent research has shown that early molecular heterogeneities between cells before polarisation can also bias cell fate. The existence of different models calls into question the role of polarisation in the first cell fate decision.
The first part of this study focuses on reconciling the polarity and heterogeneity models. It was previously thought that polarisation occurs only at the late 8-cell stage. By studying its timing in detail, it is possible to split cells into ‘normal polarising’ (NP) cells which polarise at the late 8-cell stage, and ‘early polarising’ (EP) cells at the early 8-cell stage, the latter found in approximately 20% of embryos. Although EP cells follow the canonical polarity pathway — involving the critical factors Tfap2c, Tead4 and RhoA — they have molecular and morphological differences from NP cells and are biased towards symmetric divisions and TE fate. Blastomeres with low activity of the arginine methyltransferase CARM1 prior to polarisation are known to be biased towards TE, and inhibition of CARM1, or overexpression of its substrate BAF155, increases the frequency of early polarisation. Thus, this study proposes that early heterogeneities influence cell fate by altering the timing of polarisation.
The final part of this study addresses the ability to detect polarity. Tracking polarisation over time currently requires invasive fluorescence imaging. Here, artificial intelligence is used to detect whether an embryo is polarised from unstained images, after training based on bright-field movies annotated using the corresponding fluorescence channel. The resulting model has an accuracy of 85% for detecting polarisation, significantly outperforming human volunteers trained on the same data (61% accuracy). Taken together, this study advances our understanding of polarisation and its role in the first cell fate decision, while also providing a tool for further investigation.
Approaching the Industrial Use of Plastic-Degrading Enzymes through Protein Engineering and Tandem Catalyst AdoptionsGuo, Chengzhihttps://www.repository.cam.ac.uk/handle/1810/3653502024-03-19T17:46:29Zdc.title: Approaching the Industrial Use of Plastic-Degrading Enzymes through Protein Engineering and Tandem Catalyst Adoptions
dc.contributor.author: Guo, Chengzhi
dc.description.abstract: [Restricted]