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Connecting stellar feedback in the first galaxies and cosmic reionisation
Get PDFFeedback from supernovae and the radiation emitted by stars play a pivotal role in shaping the early Universe. These feedback processes have a direct influence on gas and stellar dynamics, leaving discernible traces in observational data. For the first time, with observations from JWST, we are able to observe the high-redshift Universe statistically and at unprecedented resolution. Different modes of stellar feedback need to be invoked to explain the latest observations of reionisation-era galaxies. Therefore, it is imperative for theoretical models to forward model the impact of parameter choices and variations in feedback prescriptions on observable properties of the high-redshift Universe.
In the first part of the thesis, I present SPICE, a novel suite of radiation-hydrodynamical simulations targeting the epoch of reionisation (EoR). SPICE uses RAMSES-RT to track the propagation of stellar radiation with a focus on resolving the interstellar medium (ISM) down to ≈28pc scales. The goal of these simulations is to systematically probe a variety of stellar feedback models, including "bursty" and "smooth" modes of supernova energy injections. SPICE shows that subtle difference in the behavior of supernova feedback can drive profound difference in reionisation histories with burstier forms of feedback causing earlier reionisation. SPICE highlights that stellar feedback and its strength determine the morphological mix of galaxies emerging by z=5. While star-forming disks are prevalent if supernova feedback is smooth, bursty feedback generates dispersion-dominated systems. I present a strong correlation between galaxy morphology and Lyman continuum escape fractions of galaxies where dispersion-supported galaxies show 20-50 times higher escape fractions as compared to their rotation dominated-counterparts. This chapter emphasises the impact of parameter choices on fundamental properties of the Universe such as reionisation histories, galaxy morphologies and kinematics.
In the second part of the thesis, I model radiative transfer of Lyα and UV photons through the complex multi-phase ISM of SPICE galaxies. The goal of this project is to understand the effect of radiative transfer effects (e.g. extended emission, Lyα-UV spatial offsets) and observational systematics (e.g misplaced slits ) on the measured Lyα equivalent width (EW0) distributions. I find that spatial Lyα-UV offsets exist independently of feedback model, and are common with median values of ≈ 0.07 - 0.11'. Spatial Lyα-UV offsets are identified as the leading cause of loss of flux for JWST-MSA observations, with median pseudo-slit losses of ≈ 65% with ≈30% cases suffering from >95% pseudo-slit losses. Even in the absence of such spatial offsets, the presence of extended emission can cause median pseudo-slit losses of 40%. Additionally, complex galaxy morphologies or misplaced JWST-MSA pseudo-slit can lead to understimated UV continuum, resulting in spuriously high estimates of EW0 from JWST. Both radiative transfer effects and observational systematics strongly affect observations of Lyα emitters during the EoR.
In the third part of the thesis, I present a novel sub-grid model to predict [C II] luminosities from SPICE galaxies. I show that [C II] acts as an excellent tracer for star-formation rates for galaxies with smooth forms of feedback while bursty feedback leads to a suppression in LCII. Galaxies with smoother forms of feedback produce steeply declining radial profiles while galaxies with burstier forms of feedback exhibit relatively flatter profiles. Additionally, smooth feedback leads to broad [C II] lines with FWHMbroad > 600km/s while bursty feedback produces narrow lines FWHMbroad ≈200-300km/s. Separating galaxy populations into bulge-heavy and bulge-less, I show that bulge-heavy galaxies preferentially show centrally heavy surface brightness maps and broad [C II] line while bulge-less galaxies show flat surface brightness maps and narrow [C II] line, therefore, providing another potential explanation toward observed broad [C II] lines in high-redshift galaxies.
The simulations and the multi-wavelength studies presented in this thesis allow for a detailed study of the impact of stellar feedback on different components of a galaxy. Therefore, for the first time, SPICE enables a systematic study of relative differences in stellar feedback models and allows for robust predictions of galaxy observables in the EoR.Feedback von Supernovae und die von Sternen emittierte Strahlung spielen eine entscheidende Rolle bei der Entstehung des frühen Universums. Diese Rückkopplungsprozesse haben einen direkten Einfluss auf Gas- und Sternendynamik und hinterlassen erkennbare Signaturen in Beobachtungsdaten. Zum ersten Mal sind wir dank der Beobachtungen mit dem JWST in der Lage, das Universum mit hohem Rotverschiebungswert statistisch und mit beispielloser Auflösung zu untersuchen. Verschiedene Modi der stellaren Rückkopplung müssen berücksichtigt werden, um die neuesten Beobachtungen von Galaxien aus der Epoche der Reionisation (EoR) zu erklären. Es ist daher entscheidend, dass theoretische Modelle die Auswirkungen von Parameterwahlen und Variationen in den Rückkopplungsmodellen auf die beobachtbaren Eigenschaften des frühen Univsersums modellieren.
Im ersten Teil der Arbeit präsentiere ich SPICE, eine neue Reihe von Strahlungs-hydrodynamik-Simulationen, die sich auf die Epoche der Reionisation konzentrieren. SPICE verwendet RAMSES-RT, um die Ausbreitung stellaren Lichts zu verfolgen, mit dem Ziel, das interstellare Medium (ISM) bis auf Skalen von ≈28pc aufzulösen. Das Ziel dieser Simulationen ist es, systematisch eine Vielzahl von stellaren Rückkopplungsmodellen zu untersuchen, darunter „bursty“ und „smooth“ Modi der Supernova-Energieinjektionen. SPICE zeigt, dass subtile Unterschiede im Verhalten der Supernova-Rückkopplung tiefgreifende Auswirkungen auf die Reionisationsgeschichte haben können, wobei „bursty“ Rückkopplungen eine frühere Reionisation bewirken. SPICE verdeutlicht, dass die stellare Rückkopplung und ihre Stärke den morphologischen Mix der Galaxien bis z=5 bestimmen. Während sternbildende Scheiben bei „smooth“ Supernova-Rückkopplung vorherrschen, erzeugt „bursty“ Feedback Systeme, die von Dispersion dominiert werden. Ich zeige eine starke Korrelation zwischen der Galaxienmorphologie und dem Anteil der Lyman-Kontinuum-Photonen, die der Galaxie entfliehen können, wobei dispersionsgestütze Galaxien 20 bis 50-am Mal höhere Anteile zeigen als als ihre rotationsdominierten Gegenstücke. Dieses Kapitel betont den Einfluss von Parameterwahlen auf grundlegende Eigenschaften des Universums, wie Reionisationsgeschichte, Galaxienmorphologien und Kinematik.
Im zweiten Teil der Arbeit modelliere ich den Strahlungstransport von Lyα- und UV-Photonen durch das komplexe, mehrphasige ISM von SPICE-Galaxien. Ziel dieses Projekts ist es, den Einfluss von Strahlungstransporteffekten (z.B. räumlich ausgedehnte Emission, Lyα-UV räumliche Versätze) und beobachtungstechnische Systematiken (z.B. falsch platzierte Spalten) auf die gemessenen Lyα-Äquivalentbreitenverteilungen (EW0) zu verstehen. Ich finde, dass räumliche Lyα-UV-Versätze unabhängig vom Rückkopplungsmodell existieren und häufig vorkommen, mit Medianwerten von ≈0.07 - 0.11'. Räumliche Lyα-UV-Versätze werden als Hauptursache für den Verlust von Fluss bei JWST-MSA-Beobachtungen identifiziert, wobei die medianen Pseudo-Spalt-Verluste ≈65% betragen und in ≈30% der Fälle zu Verlusten von über 95% des Flusses führen. Selbst ohne solche räumlichen Versätze kann das Vorhandensein ausgedehnter Emission zu medianen Pseudo-Spalt-Verlusten von 40% führen. Darüber hinaus können komplexe Galaxienmorphologien oder falsch platzierte JWST-MSA-Pseudo-Spalten zu einer Unterschätzung des UV-Kontinuums führen, was zu fälschlicherweise hohen Schätzungen von EW0 durch JWST führt. Sowohl Strahlungstransporteffekte als auch Beobachtungssystematiken haben einen starken Einfluss auf die Beobachtungen von Lyαvon Galaxien während der Epoche der Reionisation.
Im dritten Teil der Arbeit präsentiere ich ein neuartiges Subgrid-Modell zur Vorhersage von [C II]-Leuchtstärken von SPICE-Galaxien. Ich zeige, dass [C II] als hervorragender Indikator für Sternentstehungsraten bei Galaxien mit „smooth“ Rückkopplungsformen fungiert, während bursty Rückkopplung zu einer Unterdrückung von LCII führt. Galaxien mit glatteren Rückkopplungsformen produzieren steil abfallende radiale Profile, während Galaxien mit bursty Rückkopplung relativ flachere Profile aufweisen. Darüber hinaus führen „smooth“ Rückkopplungen zu breiten [C II]-Linien mit FWHMbroad > 600km/s, während bursty Rückkopplung schmale Linien mit FWHM ≈200-300km/s erzeugt. Durch die Trennung von Galaxienpopulationen in bulgelastige und bulgearme zeige ich, dass bulgelastige Galaxien bevorzugt zentral konzentrierte Flächenhelligkeit und breite [C II]-Linien aufweisen, während bulgearme Galaxien flache Flächenhelligkeit und schmale [C II]-Linien zeigen, was eine weitere mögliche Erklärung für beobachtete breite [C II]-Linien in frühen Galaxien liefert.
Die in dieser Arbeit vorgestellten Simulationen und die Multiwellenlängenstudien ermöglichen eine detaillierte Untersuchung der Auswirkungen stellaren Feedbacks auf verschiedene Komponenten einer Galaxie. Zum ersten Mal ermöglicht SPICE somit eine systematische Untersuchung der relativen Unterschiede den verschiedenen stellaren Rückkopplungsmodellen und erlaubt robuste Vorhersagen über Galaxienbeobachtungen in der Epoche der Reionisation
Monitoring des klinischen Managements und Outcomes von Patienten mit Verdacht auf Kuhmilchproteinallergie
Get PDFIron fumarate nanoparticles as carriers for functional biomacromolecules
Get PDFIn recent decades, biomacromolecules like proteins, mRNA, and the CRISPR-Cas system have become indispensable in medical and biotechnological fields, paving the way for new therapeutic strategies and advancements. While proteins play essential roles in cellular processes, driving interest in them for therapy and drug development, mRNA acts as a versatile intermediary between DNA and protein synthesis, finding applications from vaccines to gene therapy. Similarly, the CRISPR-Cas system has transformed genetic manipulation, offering precise genome editing for therapeutic purposes. However, challenges like poor stability, rapid degradation, and limited cellular uptake often hinder the effective utilization of these biomacromolecules. To address these obstacles, nanoparticles (NPs) emerge as promising solutions to overcome these challenges and unlock innovative healthcare approaches.
Among the diverse array of NPs, the hybrid metal-organic nanoparticles have garnered significant attention due to their intriguing and unique properties, including tunable size, biocompatibility, and versatile surface chemistry. These characteristics render metal-organic NPs highly suitable for encapsulating and delivering biomacromolecules, enhancing their stability, promoting cellular uptake, and enabling targeted delivery. Iron-fumarate nanoparticles (Fe-fum NPs), a subclass of metal-organic NPs, possess unique characteristics stemming from their composition, which includes iron ions coordinated with fumarate ligands. These NPs demonstrate magnetic behavior, offer tunable sizes, and can encapsulate diverse cargoes. The controlled synthesis and modification of Fe-fum NPs have paved the way for their potential application across various domains in medicine and biotechnology. Although the capacity of Fe-fum NPs to store therapeutic small molecules and effectively release them to cancer cells is well established, their potential for delivering functional biomacromolecules, such as proteins and RNAs, has been relatively underexplored. The inherent pore sizes of Fe-fum nanoparticles prove insufficient to accommodate the dimensions of numerous proteins and RNA molecules, thus posing challenges for their effective entrapment within the nanoparticle pores. To overcome this limitation, in situ encapsulation of biomacromolecules in Fe-fum NPs emerges as a promising strategy, in which the nanoparticles form around biomacromolecules via a biomimetic mineralization process, ensuring a notable loading efficiency and minimal premature leakage of the biomacromolecule.
The in situ encapsulation of biomacromolecules within Fe-fum NPs needs meticulous attention to synthesis conditions. This involves transitioning to water-based synthesis methods to eliminate harmful solvents, maintaining a pH near the physiological range of around 7.4, and avoiding high temperatures. Such measures are essential for preserving these delicate biomacromolecules' structural and functional integrity, thus optimizing the efficacy of Fe-fum NPs as carriers for such molecules. Initial efforts in our study to reevaluate the synthesis according to the conditions mentioned above encountered a novel challenge: either the nanoparticles increased in size or underwent aggregation. Achieving small, uniformly sized particles is crucial to optimizing their distribution within the body and facilitating cellular uptake. Thus, the first part of this thesis focuses on investigating the impact of various synthesis parameters, including solvents, modulators, and coatings, on the size, aggregation, and degradation of Fe-fum NPs synthesized using a biomimetic mineralization approach that preserves protein integrity. Our findings reveal specific conditions that facilitate the production of colloidally stable Fe-fum NPs capable of incorporating proteins. Applying a lipid coating after the synthesis of nanoparticles stabilized the size of Fe-fum in an aqueous buffer, allowing for cellular applications. Another crucial aspect of nanoparticles is their ability to release their cargo into the cytoplasm of cells after cellular internalization. Often, internalization is mediated via endocytosis, and cytosolic release implies escape from the endosome. The endosomal release ensures the payload reaches its target, facilitating the desired biological effect. In this study, we demonstrate that lipid-coated Fe-fum NPs are internalized by cells, and intracellular release of the loaded proteins and small molecules can be triggered externally via glucose shock. Furthermore, we showed that small molecule cargo can be released from the endosome by leveraging the internal trigger mechanism provided by histidine, offering an additional method for controlled release within the cellular environment.
The second part of this thesis explores the versatility of the introduced biomineralization method involving Fe-fum NPs. It further investigates their capacity to maintain the structural integrity and operational effectiveness of diverse proteins throughout the synthesis and subsequent release process. For this, we initially demonstrated the ability of the Fe-fum NPs to encapsulate four distinct model proteins, including bovine serum albumin (BSA), horse radish peroxidase (HRP), green fluorescent protein (GFP), and Cas9/sgRNA ribonucleoproteins (RNPs). These Fe-fum NPs exhibited notably high loading efficiency for proteins, and facilitated their successful delivery into cells while maintaining protein activity. The delivery of RNPs via Fe-fum NPs resulted in efficient gene knockout in HeLa cells. Furthermore, we explored the potential of Fe-fum NPs in safeguarding proteins against harsh environmental conditions. Our findings revealed that integration into Fe-fum NPs effectively preserved and shielded the activity of RNPs even under conditions of pH 3.5 exposure and two months of storage at 4°C, conditions known to compromise the functionality of unprotected RNPs severely.
The last part of this project delved into the potential of Fe-fum NPs as carriers for RNA, with a specific focus on mRNA delivery. Using a biomineralization technique during synthesis, RNA molecules were successfully integrated into the Fe-fum NPs, facilitating their efficient delivery into cells. Moreover, the utilization of mCherry-encoding mRNA as a model RNA confirmed the successful translation and production of mCherry protein within the cells upon glucose shock, indicating the intact delivery of mRNA and subsequent translation process. These findings underscore the potential utility of Fe-fum NPs as highly effective carriers for RNA molecules, thereby contributing to the advancement of RNA-based therapeutic and biotechnological applications.
In summary, our study introduces an innovative room-temperature synthesis technique for producing Fe-fum NPs in mildly acidic aqueous settings. We demonstrate the ability to form Fe-fum NPs via biomimetic mineralization around biomacromolecules, encompassing diverse model proteins and large RNA molecules. This establishes an effective platform for delivering such molecules while preserving their functionality. Moreover, Fe-fum NPs were very efficient in safeguarding proteins from degradation during storage and against challenging environmental conditions
Residence and economic substance of subsidiary corporations in international and European tax law
Get PDFInzidenz und Management von Gefäßverschlüssen bei der Revisionsoperation von transvenösen Sonden kardialer elektronischer Devices
Get PDFDevelopment of low-scaling tensor hypercontracted electron correlation methods for energies and magnetic properties
Get PDFEver since the advent of modern day compute architectures, problems that seemed intractable in the past now have become routine operations on consumer grade hardware. To minimize the time to solution, these hardware improvements should be accompanied by algorithmic advancements. In this regard, the numerical solution of the Schrödinger equation underlying the quantum mechanical description of matter is crucial for the understanding of chemical processes, albeit being computationally expensive.
In this context, wave function methods have proven to provide high accuracy for chemically relevant systems, with one of the central limitations being the necessity to store and contract the fourth-order electron repulsion integral (ERI) tensor. To overcome this impediment, this thesis is concerned with the development of efficient algorithms to obtain lower-order approximations to the ERI tensor through least-squares tensor hypercontraction (LS-THC). LS-THC provides the unique opportunity of expressing the ERI tensor entirely in second-order tensors, thereby significantly reducing the storage requirements, while also lowering the computational cost of integral contractions, ubiquitously occurring in electron correlation methods. Due to the aforementioned advantages, LS-THC is used as a versatile tool for significantly improving the performance of a variety of correlation methods. This is demonstrated for ground state energies of perturbative methods, such as second-order Møller-Plesset perturbation theory (MP2) as well as second-order approximate coupled cluster theory (CC2). Furthermore, the resulting LS-THC-CC2 method is extended to excitation energies using the linear-response coupled cluster formalism. Besides for the calculation of energies, LS-THC is particularly attractive for adaptation to methods aiming at calculating molecular properties. From the underlying energy functional of a given method, properties can be obtained by differentiation, which in general results in a multiplication of occurring ERI types. Through the example of hyperfine coupling constants, it is demonstrated how to efficiently perform the resulting integral contractions in the THC format, when applied to MP2. Overall, the developed LS-THC approach enables the calculation of energies and first-order properties of large chemically relevant systems beyond 500 atoms.
In addition to the development of LS-THC based low-scaling correlation methods, the range of methods suitable for the accurate calculation of nuclear magnetic resonance (NMR) chemical shifts is extended. Based on encouraging results for NMR shifts at the random phase approximation (RPA) level of theory obtained by numerical differentiation, the corresponding analytic second-order derivative is derived and implemented. This represents the first formulation of an analytical second-order property for RPA as a post-Kohn-Sham method based on the adiabatic-connection fluctuation-dissipation theorem
Clinical proteomics of pneumonia — antibody-mediated immunopathology in COVID-19
Get PDFInfectious respiratory diseases comprise the 4th most fatal group of diseases worldwide. COVID-19 patients exhibit unique pathophysiology, which is not observed in pneumonia caused by other respiratory viruses or bacterial pathogens with similar severity. Most COVID-19 studies lack appropriate comparisons to other viral types of pneumonia, hindering the development of biomarkers for early identification of high-risk COVID-19 patients. This study aims to investigate the humoral immune responses and identify distinct proteomics signatures associated with COVID-19 compared to influenza and bacterial pneumonia. Moreover, the project specifically focuses on unraveling autoimmune aspects of severe COVID-19.
I applied proteomic profiling to bronchoalveolar lavage fluid (BALF) and plasma samples from pneumonia patients of the SCRIPT cohort at Northwestern Memorial Hospital (NMH) Chicago and assessed the enrichment of molecular signatures unique to COVID-19 (n=13), influenza (n=7), and bacterial pneumonia (n=6) patients at up to five time points after intubation in the intensive care unit. Emphasizing persistent proteomic signatures during hospitalization, I outlined plasma- and lung-abundant proteins and revealed upregulation of immunoglobulin production in the bronchoalveolar environment specific to SARS-CoV-2 infection.
Secondly, utilizing a single-cell multi-omic dataset of COVID-19 patients (n=102) at mild and severe stages, I identified the overrepresentation of immunoglobulin V-domains connected to COVID-19 severity. Furthermore, my findings elucidated the transcriptomic and surface protein markers of plasma cell populations, contributing to COVID-19-specific humoral immune responses observed in the BALF of Chicago cohort.
Lastly, I applied a Differential Antibody Capture (DAC) assay on two independent cohorts of acute COVID-19 patients to capture plasma antibodies that show affinity to native lung proteins. I identified 93 putative autoantibody targets specific to COVID-19 patients, with 19 targets in common in both cohorts. Among the putative autoantigens, I observed extracellular matrix, complement regulation, nuclear antigens, and immune regulatory proteins. Besides that, the dynamic changes in autoantibody patterns were correlated with clinical parameters, revealing the effect of individual autoantibodies and overall autoreactivity on severe COVID-19 immunopathology. This was demonstrated by the significant correlation of the cumulative autoantigen coefficient with a length of intubation, aspartate transaminase (AST), alanine transaminase (ALT), Troponin I, and procalcitonin, indicating prolonged recovery periods, multi-organ damage, and increased susceptibility to secondary bacterial infections.
My work improves the understanding of unique proteomic features specific to COVID-19 pneumonia, revealing the upregulation of complement cascade, platelet degranulation proteins, and immunoglobulins in the lung environment. Besides that, the research sheds light on the development of autoantibody responses during the acute phase of infection, thus providing potential biomarkers to improve the diagnosis in uncertain cases and identify severe COVID-19 trajectories at an early stage
Die Grenzen der Diplomatie
Get PDFDie spanisch-französischen Grenzräume auf dem europäischen Kontinent waren in der Frühen Neuzeit stark verflochtene Begegnungs- und Konflikträume, in denen einige Regionen und Städte teils mehrfach ihre Herrschaftszugehörigkeit wechselten. Das Buch widmet sich der Rolle der Diplomatie im Grenzziehungsprozess. Es beleuchtet am Beispiel von Abtretungen spanischer und französischer Gebiete vom Ausbruch des französisch-spanischen Krieges 1635 bis zum Ende der habsburgischen Herrschaft auf der iberischen Halbinsel 1700 Diskurs- und Raumkonstellationen in diachroner Weise. Ausgehend von den diplomatischen Korrespondenzen werden sowohl die Diskurse hinsichtlich der Herausbildung teilweise handlungsmächtiger Vorstellungen von Grenzen und Territorialität als auch die Diskurspraktiken in den Verhandlungen beleuchtet.
Isabelle Schübel studierte Gymnasiallehramt für die Fächer Französisch, Geschichte, Spanisch und Sozialkunde an der Ludwig-Maximilians-Universität München sowie der Universidad Autónoma de Madrid. Sie promovierte im Schwerpunkt Geschichte der Frühen Neuzeit und arbeitete ab 2021 als Wissenschaftliche Mitarbeiterin am Historischen Institut der Universität der Bundeswehr München. Seit 2024 ist sie im bayerischen Schuldienst tätig.In the early modern period, the Spanish-French border regions on the European continent were highly intertwined areas of encounter and conflict, in which some regions and cities changed their sovereignty several times. This book is dedicated to the role of diplomacy in the border demarcation process. Using the example of cessions of Spanish and French territories from the outbreak of the Franco-Spanish War in 1635 to the end of Habsburg rule on the Iberian Peninsula in 1700, it sheds light on discourse and spatial constellations in a diachronic manner. Based on the diplomatic correspondence, both the discourses with regard to the development of partially powerful ideas of borders and territoriality and the discourse practices in the negotiations are examined.
Isabelle Schübel studied secondary school teaching for the subjects French, history, Spanish and politics at the Ludwig-Maximilians-Universität München and the Universidad Autónoma de Madrid. She completed her doctorate with a focus on early modern history and worked as a research assistant at the Historical Institute of the University of the Bundewehr Munich from 2021. Since 2024 she works as a teacher in secondary education
Kooperation und Konkurrenz in Big Biology
Get PDFIn der vorliegenden Dissertation wurde die Geschichte und Entwicklung der Zusammenarbeit der Biologen John Sulston, zunächst angebunden am Laboratory of Molecular Biology (Cambridge, UK), und Robert Waterston, zunächst verortet an der Washington University (St Louis, USA), untersucht. Ihre Jahrzehnte währende Zusammenarbeit begann mit der Kartierung und Sequenzierung des Genoms des Fadenwurms C. elegans. Anfang der 1990er waren sie – ebenfalls kooperativ – zur Arbeit am menschlichen Genom übergegangen: Sulstons Gruppe war ab 1993 am neu gegründeten Sanger Centre (Hinxton, UK) angesiedelt und Waterstons Gruppe betrieb ab 1994 an der Washington University ein Genomsequenzierungszentrum. Gegen Ende der Laufzeit des Humangenomprojekts gehörten ihre Gruppen zu den fünf outputstärksten Laboren des internationalen Projektverbunds.
Am Beispiel dieser Arbeitsgruppen und ihrer Einbettung in den internationalen Projektverbund wurde die Forschungsfrage bearbeitet, in welchem Verhältnis das Betreiben wissenschaftlicher Kooperationsprojekte und das strategische Eintreten in Konkurrenzverhältnisse standen. Kooperation und Konkurrenz stehen als Analysekategorien im Zentrum dieser historischen Untersuchung von Interaktionsdynamiken in den Naturwissenschaften, denn es war ihre spannungsvolle Gleichzeitigkeit, die das Humangenomprojekt wesentlich prägte.This dissertation project focusses on the history and development of the cooperation between the biologists John Sulston, starting out at Cambridge's Laboratory of Molecular Biology (Cambridge, UK), and Robert Waterston, researching at Washington University (St. Louis, USA). Their intellectual partnership started with the mapping and sequencing of the genome of the nematode, C. elegans. In the 1990s they started working on the human genome, also in cooperative fashion. From 1993, Sulston and his group led the newly formed sequencing institute Sanger Centre (Hinxton, UK) and Waterston and his group started their Washington University Genome Sequencing Center in 1994. With the close of the Human Genome Project, their groups were among the most productive sequencing centres worldwide.
By looking at these groups and their involvement in the international consortium, the relationship between cooperative scientific projects and the strategic competition in the HGP was explored. In this historical analysis of the dynamics of interaction in the natural sciences, cooperation and competition were the central categories of analysis - as it was the complex interplay of both modes of interaction that shaped the HGP from the start