Background & Objectives: New therapy concepts, such as immunotherapy as well as targeted therapy with BRAF and MEK inhibitors, have significantly improved the overall survival of melanoma patients. However, about 20 % of patients do not respond to initial targeted therapy and at the same time, most of the tumors develop resistance through long-term therapy. For particular melanoma subgroups like e.g. the NRAS mutated tumors it is known, that they are associated with aggressive disease, but there is no approved targeted therapy for this subset. In clinical trials, the MEK inhibitor (MEKi) binimetinib displayed modest antitumor activity, making combinations a requisite. In a previous study, the BRAF inhibitor (BRAFi) vemurafenib was shown to induce endoplasmic reticulum (ER) stress that together with inhibition of the RAF-MEK-ERK (MAPK) pathway amplified its pro-apoptotic activity in BRAF-mutant melanoma. The present study investigated whether this effect might extent to NRAS-mutant melanoma, in which MAPK activation would be expected.

Other clinical studies in breast cancer show that PI3K inhibitors have antitumor activity. This raises the question of whether these inhibitors are also a therapeutic option for melanoma and whether a combination of them with MEK inhibitors could further restrict growth and prevent possible development of resistance in different melanoma subgroups.

Material & Methods: Melanoma cells of different genetic subtypes, as well as tissue slice cultures of patient tumors are treated with BRAF and PI3K inhibitors alone and in combination with MEK inhibitors. In addition to the investigation of cell cytotoxicity and cell cycle remainder, the altered signal transmission is detected. Furthermore, the patient cells are sequenced in order to identify mutations that promote a positive therapeutic response.

Results: BRAFi increased pERK, but also significantly increased growth inhibition and apoptosis induced by the MEKi in monolayer and patient-derived tissue slice cultures of NRAS-mutant melanoma. BRAFi such as encorafenib induced ER stress via upregulation of the ER stress-related factors ATF4, CHOP and NUPR1 and the pro-apoptotic protein PUMA. MEKi such as binimetinib induced the expression of the pro-apoptotic protein BIM and activation of the mitochondrial pathway of apoptosis. While the pan-PI3K inhibitor BKM120 is cytotoxic in almost all cell lines and patient cells, the PI3Kα-selective inhibitor BYL719 does not have an antitumour effect. However, the combination of the PI3K inhibitors with the MEK inhibitor already shows a significantly stronger cytotoxic effect at lower concentrations compared to monotherapies.

Conclusion: The data presented herein strongly encourage the clinical use of MEKi in combination with ER stress inducing BRAFi as a strategy to treat rapidly progressing NRAS-mutant melanoma; the combination of PI3K inhibitors with MEK inhibitors could be a new therapeutic option for BRAF wildtype melanomas.

Through the Athena program, I hope to connect with women in similar positions and stages of life and advance my own career in an independent position by having the opportunity to participate in career planning coaching and future workshops. I also think it is immensely important, especially in today's world, for women in science to form good networks and encourage and promote each other.

In grocery retailing, sales promotions are a key element of the marketing mix. The most
frequently used promotion tools are price cuts and store flyer advertising. In Germany, for
instance, about one fourth of grocery sales volume was sold on price promotion in 2017
(Nielsen 2018), and store flyers accounted for one third of retailers’ advertising budgets (EHI
Retail Institute 2016). However, these tools play different roles in the promotion mix: store
flyers draw attention to the product while price cuts provide an incentive to buy the brand
(Zhang 2006). Consequently, both instruments generate large lifts in sales (e.g., Ailawadi et
al. 2006). Despite retailers’ intense use of both tools, it is still unclear whether and when it is
beneficial for retailers to combine price cuts and store flyer advertising for a brand, i.e., to use
both tools simultaneously as opposed to using them in separate weeks. This decision depends
on the presence and nature of synergy effects between price cuts and store flyers (Zhang
2006). Therefore, we systematically investigate synergies between price cuts and store flyers
for a broad set of brands in multiple categories across six leading German retailers. Thus, our
findings have important implications for the coordination of promotion activities.
I am thankful for the support through Athene. I value the training and workshops Athene is
providing as well as the great transdisciplinary discussion with my fellow Athene members.

For more information visit my personal website: https://www.wiebke-keller.de

Recent progress in machine learning for healthcare has been extraordinary, and some tools are approaching human-level performance in controlled settings in application areas such as ophthalmology or cancer detection. However, major hurdles still obstruct the wide adoption of machine learning in clinical practice: When machine learning is applied, its outputs are often used to inform treatment decisions. ML algorithms therefore have the potential to cause harm to the patient and are subject to regulations to ensure their safety and effectiveness.

As the use of artificial intelligence in medicine in practice is relatively new, developing methods for demonstrating its safety and effectiveness is still an active area of research, and the regulatory pathway for AI in medicine is currently being shaped. One crucial aspect to certifying a ML algorithm is the clinical validation of its performance, where the tool is applied to validation data obtained from clinical studies. Ensuring that the performance of a ML system then generalises to previously unseen real data is difficult, as these systems are famously brittle and are known to fail silently and catastrophically.

My research focuses on methods to ensure generalisation of performance claims from clinical validation studies to the real use scenario of medical machine learning applications. This is crucial to their certification and safe use. More specifically, here it will be largely studied on applications in ophthalmology due to the close ties between my host group and the department of ophthalmology.

The Athene Grant supports my career development with individual coaching sessions and workshops and provides a valuable network with peers throughout Tübingen.

https://www.eye-tuebingen.de/berenslab/members/lisa-koch/

My primary mathematical background relies on real algebraic geometry. During the years, I have been able to see that this field is strongly related to tropical, enumerative and symplectic geometry. Therefore, I am directing my research towards some questions which live in the intersection of these different and, at the same time, similar subjects. I became a Research Postdoctoral Fellow at the University of Tübingen in April 2021. I am part of Professor Hannah Markwig's group of Kombinatorische Algebraische Geometrie at the Faculty of Mathematics. I would say that it takes very little to make a mathematician happy, we do not need experimental laboratory equipment or special working spaces to do research. On the other hand, a mathematician needs the possibility to have personal contact with other mathematicians. Meeting new people at a conference, have a concrete feeling of what a colleague is really saying to you and feel free to stay together many hours without routine life in the way are completely off charts if you try to do things online only. It is not possible to find a satisfying surrogate for any of these human experiences, nothing can replace in person meetings and how relevant they are for every mathematician to pursue her/his research.
Therefore, even if Tübingen is an excellent environment to do research, I have applied for an Athene Grant in order to be able to travel more, especially after the pandemic break. I have been exploiting a lot this opportunity and I am very glad to be able to work with my collaborators and make new ones.

http://matilde.manzaroli.perso.math.cnrs.fr/pdf/cv/CV_manzaroli_english.pdf

In my habilitation I investigate political negotiation processes and knowledge structures in the collective solution of complex environmental problems. Climate change, biodiversity loss, and air pollution are currently among the greatest environmental threats to humanity. Countless scientific studies underpin this impending ecological catastrophe. If we have had this knowledge for decades, why is it still so difficult to avert these life-threatening dangers? Which influencing factors are important in the political decision-making process? Why does scientific knowledge seem to have little or no influence on political decisions? Is it easier to set the political course towards more sustainability at the local level when environmental impacts are directly visible? Which actors and networks are crucial in the policy process?

My work is based on a relational view based on social network analysis. The network relations of actors in combination with attributes (such as organizational affiliation, diversity, political level) are informative for the analysis of negotiation and policy processes. Added to this is a discourse analytic approach, i.e., the negotiation of policy problem-solving approaches by actors in different discourse arenas based on arguments, beliefs, and ideas. My findings and publications to date reinforce my belief that my approach can contribute to exploring these central issues of scholarly and societal relevance.

My motivation for the Athene Grant Program: In the final phase of my habilitation and the subsequent application phase for a professorship, I would like to receive support, networking with other scientists, and advice (e.g., on third-party funding applications and strategies for applications). The Athene Grant Program is an excellent opportunity for me as a scientist and mother of three children to strengthen my career development through coaching.

Bacteria are fantastic at adapting and thriving in the most challenging environments. This capacity of bacteria and other microorganisms to adapt, rest on their ability to react and coordinate multiple environmental and intracellular signals. Many intracellular signaling functions are carried out by metabolic intermediates, which are not only involved in self-regulation, but also control cell to cell interactions. In this project, we seek to identify and understand how metabolites input signals into bacterial regulation systems.  

We employ Escherichia coli, a genetically versatile bacterium, along with a CRISPRi system to study gene expression on a genome-wide scale. In combination with metabolomics and proteomics methods, these tools allow us to characterize metabolic genes that are important for growth, and ultimately permit the identification of intermediates that are involved in bacterial regulation. We anticipate the application of these tools to study how metabolic processes shape bacterial communities and endow advantages to bacterial pathogens in the context of disease. 

I applied to the Athene program to access financial support to continue with my research interest, and greatly appreciate the opportunity it has given me to network and learn from their workshops.

Link: www.linkmetabolism.com/team2

The asymptomatic nasal carriage of Staphylococcus aureus increases the risk of infection, urging the identification of the factors that enable S. aureus to colonize the nasal cavities. In this context, the role of the resident microbiota in creating favourable or hostile nutritional milieu for S. aureus has long been neglected. Competition for resources is known to shape pathogen colonization within the gut and skin microbiotas, suggesting that a similar phenomenon could impact S. aureus persistence within the nares.

My research focuses on identifying the main nutritional interactions occurring between nasal commensals and their impact on S. aureus physiology. To this end, we combine approaches of sequencing, metabolic screening, co-cultivation and time-lapse microscopy using a collection of 291 nasal bacterial isolates newly assembled. We expect to reveal the nasal species and nutritional exclusion mechanisms restricting S. aureus proliferation, thus paving the way for the development of new strategies to prevent S. aureus colonization of the nasal cavities.

The support of the Athene grant allows me to develop complementary competences in research management, career planning, scientific communication, but also to expand my scientific network and advance my academic career. This is possible thanks to the wide range of events funded or organized by the program, as participation in workshops, conferences and visits to laboratories led by internationally recognized women. 

Online CV: https://www.linkedin.com/in/laura-camus-5325611a4/?locale=en_US

Human reproductive failure (including infertility and miscarriage) affects one in six couples globally and is becoming a serious socio-economic concern. Human pregnancy simply requires implantation of an embryo into the womb lining - yet, many unknown or deregulated factors may prevent implantation from occurring. Without understanding the root cause, treating reproductive failure often becomes a guessing game. Most implantation-related events remain uncharted territory, making implantation a true ‘black box’ in biology.

My research focuses on miscarriage, when an embryo or fetus doesn’t survive past the 20th week of pregnancy. Miscarriage usually happens early in a pregnancy — 8 out of 10 miscarriages happen in the first 3 months.  Lots of people experience this kind of pregnancy loss. In fact, 10-20% of pregnancies end in miscarriage. But even though miscarriage is common, it can be emotionally difficult. It can be difficult to know exactly why a miscarriage happened and research in this area is limited.

The central questions to be addressed in my research, are, firstly how does the womb lining ‘sense’ embryos and, secondly how is this selection influenced by the maternal uterine microenvironment. Combined with next-generation single-cell sequencing (NGS), live-cell calcium influx measurements, super-resolution imaging and multi- Crispr/Cas9 genome editing; we propose to (I) integrate maternal-embryonic phenotypic-genomic signatures to stratify the risk of implantation failure; (II) reveal to what competency clues are given to the mother.

Good professional networking is particularly important because of the broad range of methods and disciplines covered by this project. The Athena program provides me with exactly the support I need to develop my scientific career through workshops, exchange of experiences and financial support.

https://www.medizin.uni-tuebingen.de/de/das-klinikum/mitarbeiter/profil/1806

In the electromagnetic spectrum, the frequency band of ~0.1 – 10 THz has for a long time lacked practical emitters and detectors. This has commonly been called the ‘Terahertz gap’. Developing practical THz technology would enable exploiting the unique properties of THz radiation, namely strong and non-invasive penetration, and frequencies resonant with absorption bands of many useful materials and molecules. Fortunately, the last two decades have seen a tremendous technological progress of THz sources, like the development of quantum-cascade lasers (QCLs). In contrast to this successful effort of developing new sources, there has been a severe lack of practical detectors.

 In my research, I seek to address this technology gap by bringing together different fields and techniques to develop a type of THz detector using optical spectroscopy on an atomic vapour with Rydberg atoms. This will provide in-situ optical measurement with sensitive and narrow-band detection as these atoms act as antennas to provide precise electric field measurements. The detections will be tested with a QCL source.

The Athene grant support my research by allowing me to attend conferences where I can present my work and to hire a research assistant who can support my family-work balance. Besides the grant provides me with training, workshops, personal coaching, and the opportunity to network with other female University.

Personal website:

laratorralbocampo.academia.edu

My habilitation project is dedicated to the first comprehensive treatment of the previously unknown corpus of Sumerian mock hymns, which were composed in Southern Iraq around 4.000 years ago. At least four of these hymn parodies are currently known, but only two are available in critical editions and translations. Based on first or new critical editions of all texts, this project aims at the first systematic investigation of this unique text corpus.

The mock hymns are characterized by the fact that they emulate the form and style of hymns but fill it with exclusively derogatory content. Songs of praise hence turn into songs of abuse, containing abundant insult against ugly, evil and incompetent characters. As a result, they also develop an apotropaic effect. Apart from parallels with incantations, intertextual allusions to nearly all genres of Sumerian literature can be found: they range from proverbs to ritual lamentations, prayers, epics and love songs.  The mock hymns thus provide important new insights not only into the reception of traditional Sumerian literary works from the 3rd millennium BCE, but also in the practices of text production in the intellectual milieux of Babylonia in the early 2nd millennium BCE.

The Athene programme not only supports my project financially, but also offers opportunities for networking within the University of Tübingen and beyond. This is extremely valuable, especially during the pandemic.

The project investigates the narration of the recent past of Eastern and Central Europe in the works of the main representatives of Polish contemporary nonfiction literature called “gonzo”.  I am analyzing how Polish gonzo authors construct narrations on the recent past in a manner that escapes the dominant historical discourses.

Gonzo nonfiction, emerging from American New Journalism in the mid- and late 1960s, is characterized by its subjectivity, first person narrative, colloquial language, perspective ‘from below’, full dialogues, and sarcasm. In Poland, gonzo travelogues are successful in composing literary stories that, thanks to their metonymic potential, can call into question dominant discourses concerning the recent history (including the recent ‘illiberal turn’ in politics). The authors focus on local curiosities, unexpected phenomena of the borderland provinces, nationalisms of ‘small nations’ and their unusual manifestations, and the paradoxes of established discourse categories (e.g. ‘Easternness’). The gonzo stylistics enable them to mix uneasy topics with irony and to focus on the narrated story itself.

In my work, I am focusing on how Polish gonzo authors reuse and dispel stereotypes concerning class and gender identities and play with issues concerning ethnical, national, and political identities. I am taking into consideration masculinity studies, the theory of historiography (‘revival of the narrative’), the spatial turn, and postcolonial studies.

Zum Athene-Stipendium:

I firmly believe that the interdisciplinary networking and the mentoring prospects within the Athene program

 will constitute a significant enrichment for my research opportunities and career planning. 

I am currently conducting ethnographic research with people living with dementia in care homes on practices of liturgy. More specifically, I focus on how ‘dementia’ is constructed, maintained, and at times also made irrelevant in contexts of ‘worship’. While professional discourse in the field primarily focuses on dementia as a condition which necessitates professional action very different from what might be expected in contexts of ordinary parish work, I am interested in the fabrication of this difference as a socio-material practice: In what ways do people, discourses, things, space, sound, smell etc. interact in bringing about the dementia/non-dementia binary in contexts and settings of pastoral care? How does the binary operate and to what effects? In line of approaches which combine practice theory with New Materialist concepts the project explores the various venues and complex avenues of ‘doing dementia’ and ‘doing worship’, suggesting that both occur as inextricably interwoven events.

The portrayal of the nasal microbial interactome: Mathematical and Biological challenges of the nasal microbiome landscape

As the interface between the external world and the human body, the human nose is the main entry point for numerous pathogens and commensal bacteria. The composition and homeostasis of the nasal microbiome profoundly impact the development of infectious diseases. Surprisingly, the contribution of many nasal microorganisms to human health remains undiscovered. The severity of world-wide infections with hardly treatable pathogens motivates us to construct a community-level network of microbial species that populate the human nose. Our large-scale network reconstruction approach started with an extensive literature search for observed nasal microbes. By applying an analysis tool on the collected data, we created an initial interaction network of nasal microbes. This network became the foundation for formulating a mathematical model to accurately estimate the interaction parameters and get an efficient and detailed biological interpretation of the nasal microbiome. Next, we will examine the mathematical behavior of the network and its stability in response to perturbations. Furthermore, experimental data will be used to validate the predicted results. Our endeavor will ultimately deepen our understanding of the interactions within the nasal microbial community and their role in homeostasis, health, and disease. This project is driven by the vision of a future in which, based on modeling, the interspecies interactions can be controlled to benefit human health. The Athene grant can move this project forward in a timely manner. I am thankful for the beneficial training, workshops, and personal coaching about fundamental career development that it provides.

https://uni-tuebingen.de/en/134065

Aptamer-based therapies for neurodegenerative diseases of the retina

Degenerative processes of the retina, as they occur in age-related macular degeneration, glaucoma or retinitis pigmentosa, result in the death of essential neuronal cells such as ganglion cells or photoreceptors and can thus lead to blindness. Due to the multifactorial causes and the various genes involved, specific targeted therapies are often difficult in these diseases. Therefore, treatment is usually only symptomatic, e.g. by prevention or reduction of cell death. Aptamers, which specifically bind to their target molecules and thus exert neuroprotective effects, offer the possibility to develop new therapeutic options for retinal diseases. The project aims to further our understanding of the underlying molecular pathomechanisms of retinal degenerative diseases and to generate novel therapeutic options based on two aptamers. The first aptamer activates the signalling cascade of neurotrophic growth factors via receptor binding. Growth factor-based therapy is also an approach that has been successfully investigated experimentally in many other neurological diseases. The second aptamer binds and inhibits a central regulator of apoptosis and is thus expected to reduce the final cell death pathway. Various retinal organ culture models, which can be used to simulate the pathogenesis of these diseases, are used to test the neuroprotective effect at the molecular and physiological level. Good professional networking is particularly important because of the broad range of methods and disciplines covered by this project. The Athena program provides me with exactly the support I need to develop my scientific career through workshops, exchange of experiences and financial support.

http://www.eye-tuebingen.de/clinical-research-labs/schnichelslab/members/jose-hurst/

GRAPHTEC project. “Graphite”-Painted Pottery from the Neolithic/Chalcolithic Balkans: An Archaeometric Investigation of Ceramic Technology and Innovation in Prehistoric Europe

Graphite decoration on ceramic vessels is a distinctive phenomenon spread over most of the Balkans during the 5th millennium BC. By focusing on Late Neolithic and Chalcolithic ceramic assemblages from different key archaeological sites in the Struma valley (Greece and Bulgaria) and its broader region, this interdisciplinary study aims to provide for the first time an innovative and original contribution to our understanding of the technology behind graphite decorated pottery and its network of circulation. Processes of adoption and transfer of technology and ideas are crucial concerns for present-day archaeology. Therefore, their study allows to investigate cultural and economic networks amongst people, especially by looking at the underlying technological traits and abilities of social groups. Overall, by focusing on themes like innovation, processes of adoption, and transfer of technological knowledge, this project will provide a body of reference work not only for those studying pottery from the Prehistoric Balkans, but also for the broader archaeological community.

The Athene programme made it possible for me to receive initial support to begin this project and offered excellent personal coaching in career development. In addition, it gave me the unique chance to broaden my networks with other female scientist across different disciplines.

https://silviaritaamicone.academia.edu/

The so-called ‘post-classical’ Sagas of Icelanders, thought to be written in the fourteenth and fifteenth centuries, have received little scholarly attention in the past. Previous generations of critics have tended to demean them as the inferior products of a degenerate late medieval society. They have been unfavourably compared to ‘classical’ Íslendingasögur and fornaldarsögur alike, as though they were an inferior combination of the two, leading modern audiences to project their expectations onto narratives that nevertheless do not adhere to simple taxonomies and preconceived notions of genre. This study brings the complexity and subversiveness of these narratives to the fore. As rogues within the canon, they are troublesome to scholarship, and because they challenge the established notions of what makes an Íslendingasaga, new models of reading them have to be developed where old ones will not serve. Based on a critical appraisal of conceptualizations of canon and genre in saga literature, I suggest a new reading of the relationship between the individual, paranormal, and social dimensions, a triangulation that forms the foundation of these sagas. Drawing on a multidisciplinary approach informed by perspectives as diverse as possible worlds theory, gender studies, and social history, the ‘post-classical’ sagas are not only read anew and integrated into both their generic and socio-historical context — they are met on their own terms, and they are at last allowed to speak for themselves.

I applied for the Athene programme because the many years I spent abroad have taught me that international cooperation and networking are one of the most important parts of academic work. Moreover, as a chronically ill woman, the added funding allows me to hire a research assistant who supports me in my work.