Dragon09/odtu_chatbot huggingface dataset:
unraveling the natural complexity of protein secretion to optimise novel robust yeast strains

protein secretion is a universal trait among organisms involving multiple steps of quality control sorting trafficking and export as well as various organelles numerous pressing challenges faced by society can be addressed by thoroughly understanding protein secretion disease mechanisms can be elucidated new antimicrobials can be discovered and highvalue proteins can be produced however exactly because of its complexity a full mechanistic understanding of protein secretion is still lacking impeding full exploitation the yeast saccharomyces cerevisiae is a promising model organism for studying protein secretion and is also a major expression host for industrial heterologous protein production so far research has only focused on a few lab strains that are inefficient protein secretors and that do not fully represent this yeasts natural biodiversity my preliminary data show that properties considered to be optimal in lab strains often are inferior to those observed in some other more wild yeast herein i propose that natural s cerevisiae strains can have more efficient protein production and secretion pathways and that the responsible alleles can be identified and exploited creating a robust proteinproducing strain in proteoyeast i will combine my skills in omics analyses and systems biology with the host labs qtl mapping expertise unique yeast collection 1200 strains and advanced robotic systems to address the existing knowledge gap this work will be divided into three parts 1 highthroughput investigation of the natural biodiversity for protein secretion in a highthroughput manner 2 round robin qtl approach to identify novel alleles affecting protein secretion and 3 development of robust strains for hightiter secretion of addedvalue proteins todays urgent demand for a sustainable biobased economy combined with progress in laboratory automation and systems biology make this project timely and fitting to societal needs
hedgea high cell density engineering for the production of recombinant adenoassociated virus raav

hedgea will address one of the current main challenges of biopharmaceutical production the scalability of the recombinant adenoassociated virus raav production process big data approaches like transcriptomic and proteomic analyses will be used together with synthetic biology tools to engineer cell cultures and improve raav production the objectives of hedgea are to design 1 a suitable cell platform to sustain transfection at high cell densities and 2 a scalable upstream bioprocess to improve raav biomanufacturing access to gene therapy is currently extremely limited due to the high cost of producing raavs leading to expensive treatments and making it virtually inaccessible for the general population or even for diseases requiring high dosage the main limitation is the poor scalability of the current raav production process hedgea will delve into the molecular limitations of the cellular platform and provide a solution to reduce costs increase titers and help raavbased gene therapies reach the wider population a costeffective production process for raavs will have a high impact in eu competitiveness as it will open the market for countless gene and cell therapies that are currently nonviable due to the required titers to reach clinical trials hedgea will present the perfect opportunity for the applicant to join a cuttingedge working environment to fulfil his potential in cell engineering and bioprocess development the host centre dtu copenhagen is a leading expert in the field and can provide the essential network to undertake a project like hedgea bridging academic research and its industrial application
the economics and politics of alternative realities

many people hold systems of wrong beliefs which combine into a semicoherent alternative reality based on the sinister motives of influential actors i build models of the supply of and demand for such alternative realities the key idea is that people believing in alternative realities misperceive not only features of the environment but also the incentives of other actors applications of my supply side framework include the analysis of political conspiracy theories that serve to discredit the intellectual elite fear mongering to prompt mobilization in a conflict and antistate narratives that serve to generate political support for fiscal conservatism my demand side approach formalizes the idea that individuals believe in alternative realities to protect a set of core beliefs fundamental to maintain their preferred identities these models explain stylized facts in domestic and foreign politics and generate new predictions which i test
drivers and origins of highaltitude precipitation on the third pole

asias mountain ranges are the worlds most important water towers often referred to as the planets third pole precipitation in these mountains feeds glaciers and snow fields and generates river flow which sustains millions of people downstream precipitation also triggers natural hazards such as floods landslides and avalanches which cause enormous human and economic losses despite the importance of highaltitude precipitation we lack a fundamental understanding of the mechanisms that control its distribution and how it changes we need this to elucidate the water cycle at the third pole drop will close this knowledge gap by showing how the mountains feedback from land surfaces and largescale circulation control the magnitude and spatiotemporal distribution of highaltitude snow and rain new field observations at extreme altitudes and stateoftheart atmospheric modelling will provide a comprehensive picture for the entire third pole at a wide range of scalesat the smallest scale a highaltitude ice core and meteorological observations will provide key insights into past accumulation trends at the valley scale i will combine dense observations of precipitation and highaltitude snow accumulation with atmospheric simulations to gain insight into snow and rainfall patterns at the scale of the entire third pole i will conduct stateoftheart atmospheric model experiments combined with insitu observations in regional transects and remote sensing to understand how the extreme topography land surface feedback and moisture recycling control snow and rain patterns drop will provide a longawaited scientific step forward in understanding mountain precipitation in a region where this is of vital importance for water security and disaster risk reduction for millions of people
rediscovering the wanderer restoration of sympathicovagal disbalance in irritable bowel syndrome by neuromodulation a novel therapeutic concept

common colloquial phrases like gut feeling or butterflies in my belly are not just idioms but reflect on the unique communication between gut and brain the principal interface for this interaction is the autonomic nervous system a largely subconscious system that manages bodily functions through a delicate balance between its two branches the sympathetic and parasympathetic nervous systems the vagus nerve is the main component of the latter diminished vagal tone resulting in increased sensitivity to pain is characteristic for many chronic pain disorders including irritable bowel syndrome ibs people with ibs have frequent and often severe abdominal pain while its etiology remains poorly understood ibs is now assumed to be caused by a malfunctioning of the gutbrain axis often manifesting in sympatheticovagal disbalance however no established therapies currently target this neurological disturbance i hypothesize that restoring the sympathicovagal disbalance through autonomic neuromodulation can be an important novel therapeutic target in ibs to achieve this i will use transcutaneous electrical vagus nerve stimulation via the auricular nerve i will also develop a novel multimodal vagalautonomic neurosignature through combining actively and passively recorded biometrics and highpower field neuroimaging this profile will allow identification of patients who could benefit from the new treatment approach simultaneously i will investigate mechanisms of action in a comprehensive manner using experimental models and tools i have previously developed my project is foreseen to fundamentally change the therapeutic landscape of ibs and other pain disorders by providing highquality clinical and mechanistic evidence for the efficacy of vagal neuromodulation identifying a neurological signature of patients that likely benefit from this approach would represent a major breakthrough in individualizing therapeutic efforts in ibs
building capacities for the climate neutral and smart cities mission

capacities will shape a european environment conducive to urban climate neutrality transitions for national regional and local authorities the project aims to initiate and strengthen national change processes by establishing national networks and governance structures and by providing dedicated support for public authorities to put enabling conditions and measures for cities in place for achieving the cities mission to achieve this ambition the capacities consortium represents 15 european countries who have committed to initiative and strengthen national change processes by ministerial or other high political level capacities thereby build on a wellestablished network of national authorities national ministries and agencies responsible for urban transition with its relevant urban stakeholder organisations beyond the consortium partners and countries to all project partners capacities offers dedicated services to in support of national change process first a transnational alliance for public authorities to exchange learn and inspire each other in their transition towards climate neutral cities second support in prototyping innovative multilevel and cross sector governance structures third thematic capacity building for public authorities and support in taking effective local action and fourth strategic synergies and access to other initiatives that address the climate neutral and smart cities mission
mimicking bacterial middle ear infection in the lab

bacterial infections in the human body mostly involve biofilms locally dense populations of bacteria that are extremely difficult to treat with antibiotics understanding antibioticbiofilm interactions is crucial if we are to design better antibiotic treatment regimes to avoid the emergence of antibiotic resistance in biofilms bacteria are surrounded by a biopolymer matrix which can inhibit the motion of antibiotic molecules leading to complex diffusive behaviour yet it is not known how these biophysical matrixantibiotic interactions influence bacterial killing in a spatially complex infection model answering this question is the objective of my proposal i will set up a lab model that mimics acute otitis media bacterial infection of the middle ear and i will use advanced microscopy methods to track antibiotic molecules as they interact with bacterial biofilms i will answer the following questions a what is the spatiotemporal distribution of antibiotic molecules in the biofilm and b what is the effect of biofilm structure on the antibiotic response at the singlecell level after establishing materials and protocols objective 1 i will use fluorescencecorrelationspectroscopy fcs to characterize the spatial distribution of antibiotic molecules objective 2 next i will use stateofart 2d stedfcs method combination of fcs with stimulatedemission depletion microscopy to track in unprecedented detail how antibiotics kill individual bacteria within a biofilm objective 3 finally by tracking bacterial growth over long times i will determine how antibiotic resistance emerges in these spatially complex biofilms objective 4
instrumentfree 3d molecular imaging with the volumetric uminetwork explorer

current molecular imaging and spatial transcriptomics methods are limited in throughput and affordability and are constrained by inherent 2dimensionality we propose the volumetric umi network explorer voluminex a 3d implementation of sequencingbased microscopy this radical alternative to optical imaging builds spatial molecular maps by sequencing dna barcode networks where each node is a clonally amplified dna patch and each edge indicates internode proximity the resulting network reveals gene identities along with their locations without a reference map we propose an endtoend pipeline starting with a tissue followed by enzymatic processing steps and ending with sequencing and a computational reconstruction to form a molecular image we envision this procedure as an offtheshelf commercial kit offering an inexpensive alternative to advanced imaging instrumentation expanding access to more researchers and potentially even clinical diagnostic settings we are led by a stockholmbased techdev team with seminal contributions to the field of sequencingbased microscopy and a stockholmbased company single technologies ab with a proprietary 3d sequencing device uniquely suited for validating our technology we have partnered with an utrechtbased team of life scientists to develop and deploy our technology on organoids a rich controllable model tissuelike system perfect for exploring 3d biological imaging finally at the heart of the project are undiscovered laws and physical principles which we aim to uncover and exploit with our parisbased team of theoreticians who will develop optimisation graph theory and machine learning algorithms to tackle the challenging computational problem of spatial reconstruction presented by sequencingbased microscopy through voluminex we aim to kick off a new era of molecular imaging where comprehensive spatial and transcriptomic data is accessible affordable and 3dimensional
pipeline for rapid diagnostics of emergency transboundary infectious diseases

it has become apparent that the ease of travelling global warming and changes in the environment accelerate the spread of infectious diseases of zoonotic origin international collaboration is essential to impact on the control of disease epidemics and as the covid pandemic has shown rapid diagnostics are one of the main pillars preparetid will target infectious agents of three types an ongoing neglected epidemic an ongoing emerging epidemic and an ongoing elimination drive the aim is to develop the necessary in vitro diagnostic tools for preparedness needed in case of the emergence of infectious agent x preapretid is a multidisciplinary research consortium drawn from 16 european and 4 international research organisations and smes biomedical researchers will work alongside epidemiologists clinicians veterinarians and software engineers to implement a pipeline from a mobile suitcase sequencing laboratory with a simple bioinformatics to a fieldable rapid nucleic acid extraction procedure a mobile smartphone linked molecular pointofcare and a multiplex pcr onehealth surveillance platform and a one health digital platform these will provide innovative diagnostic solutions for crossborder health threats at international level preparetid will increase the accessibility to novel diagnostics for detection of pathogens with pandemic potential the consortium will deliver pointofcare and mobile diagnostics which can be easily deployed and mass produced in case of an epidemic or pandemic
dstrain data science postdoctoral training programme

dstrain is a 5year postdoctoral programme that will award 36 postdoctoral fellowship positions of 36 months each in two calls over the programme period within the overarching frame of data science the programme will train researchers and innovators with disciplinary interdisciplinary and transferable skills and a foundation in data science methods enabling them to become europes digital leaders across disciplines and sectorsdata science ds is a fastgrowing scientific area of high importance playing a central role in all scientific investigations and are essential to innovation in almost all domains across society data science underpins the majority of todays technological economic and societal feats increasing amounts of data offer enormous opportunities but only to those who are able to harness them in order to utilize these opportunities skills and competences in data science are necessary such skills will play an essential role in shaping future technological developments there is a massive interest both in the public sector and in the industry for candidates with excellent qualifications in data science combined with the ability to use these skills in crossdisciplinary projects the dstrain programme will facilitate groundbreaking research by emphasizing interaction between data science computational science natural sciences and technology the programme will develop new research and educational strategies that will serve society at large the postdoctoral fellows will be integrated in research groups across scientific disciplines where there is an urgent need for computationally skilled researchers the research groups provide excellent research environments and supervision enabling worldclass research innovation and digital infrastructure models for crossdisciplinary collaboration and training in research including computational and transferable skills the dstrain program also includes a range of crosssectorial secondments
new generation of substrates to harness the full power of microorganisms

bac3gel is a biotech company that develops and distributes advanced substrates to harness the full power of microorganisms bac3gel substrates are the first that combine threedimensionality with gradients of oxygen nutrients and physical properties to allow the growth of complex microbial communities and currently unculturable bacteria that depend on these microenvironments to thrive our advanced substrates have the power to revolutionise the status quo of microbiology and unlock innovative bacteriabased solutions to solve challenges across multiple biobased industries bac3gel mission is to ultimately foster the discovery of new antibiotics and biobased solutions to feed the evergrowing demand for innovative treatments as well as the development of microbiomemodulating drugs to address 90 of diseases linked to human microbiome imbalance
euconexus enables promoting excellence through innovative ecosystems

the concept of euconexus enables is built upon the strong foundation of our alliance within the joint research area as an excellent network for cooperation between the partners with several points of gravity such as the 4 joint research institutes an outcome of h2020swafs project coastal engineering institute environmental sciences and biodiversity institute life sciences and biotechnology institute social culture and human sciences institute and the doctoral school framework of euconexus european university the project is devoted to promote scientific and academic cooperation between the members of the alliance in the same time with an effective implementation of era policy agenda main objectives using as thematical background 4 major challenges the project is dedicated to achieve specific objectives that are aligned with mostly all of the era goals the scope of the euconexus enables project is to create the framework of an innovative ecosystem promoting sustainable synergies between the alliance and its partners such as the fellow municipalities other stakeholders in order to develop long term solutions for smart urban coastal sustainability challenges based on the digital twin approachthe project is focused on one hand to raise excellence in value creation through deeper and geographically inclusive cooperation and on the other hand to the societal based topics and needs coming from our supporting ecosystems of stakeholders the project will also offer training and capacitybuilding programs for researchers promoting a culture of collaboration innovation and continuous improvementthrough hackathons capacity building and knowledge exchange activities the project will engage experts researchers and stakeholders in the development and implementation of innovative digital twin solutions citizen engagement in participatory science activities will also be facilitated encouraging evidencebased policies and interventions
mapping change in islamic law rules and practices

this project launches a historical inquiry into the phenomenon of legal authority in muslim religious law sharia a term that designated for centuries the muslim jurists law is undoubtedly a major issue in the muslim world and to a different degree in western societies today as representing gods law in muslim believes sharia is perceived as unchangeable and in western scholarship often as a deontology mcilrap takes a radically new approach in explaining the obvious paradox between timeless law and observable legal adaptations by studying legal casuistry not single rules in casuistry rules are fixed as laws and adding rules for specific or other cases limits existing rules application and allows for different solutions which may be viewed as a legal change to describe the casuistry of the jurists law for the first time in detail mcilrap creates a new method of mapping rulings in context thousands of law books and other juridical texts constitute relics of legal thinking in its redaction period mcilrap pioneers a comprehensive survey of this source material that necessarily proceeds at different analytical levels by a widely cataloguing works according to author and subjectmatter b the indepth mapping of juridical rules in selected law books and c determining the conceptual links between juridical rules and detailed real case practicesthe project creates a dataset from original source material and devises tools for visualising legal casuistry by its research on islamic law mcilrap provides evidence for historical law developments that turned sharia formerly only revealed law into a juridical rule system that lasted until the 19th century the centurieslong impact of sharia law on muslim culture is what has triggered todays understanding of sacred sharia laws in the quran and prophetic tradition milrap will open new paths of inquiry create methods and data and by this fundamentally change the study of islamic law
patientcentered care for vestibular disorders

despite receiving little attention vestibular disorders result in loss of vestibular inner ear function and create costly health disparities onethird of the population experiences some form of vestibular loss vl that presents with a mix of symptoms from dizziness to brain fog that reduces both quality of life and workforce capacity and for unknown reasons is more prevalent and disabling in women for most individuals with vl the underlying etiology is unknown and management is insufficient due to its prevalence disability and poor management vl results in aggregated costs likely exceeding 6 billion per year in europeto combat the burden of vl and address the need for innovation along the entire chain from basic knowledge to new treatments we mobilize an international team of 13 academic and 9 nonacademic partners who unite specialized scientific and clinical expertise advances in computing device engineering and remote management platforms and clinical and patient networks we synergize these resources to deliver stateoftheart training necessary for 10 doctoral candidates dcs to innovate the new tools knowledge approaches and devices essential to understand the etiology of vl capture and interpret characterize the relevant symptoms of vl and expand treatments to restore vestibular function with collaborative impact activities we additionally train dcs to enable diverse end users to adopt use and further innovate these tools and stakeholders to better advocate for future innovationby training new leading experts we aim to advance patientcentered care of vl and moreover reduce healthcare costs and promote sustainable green healthcare systems while also enhancing workforce and innovation capacity for individuals with vl and in the emerging academic clinical and industrial sectors focused on the care of vl provide will be a model for future networks tackling challenges in healthcare and striving for health equity