1^st EMBL/DFG Women in Science Network Conference Heidelberg 2016

Introduction

The WiS conference 2016 offered an inspiring forum for female scientists to meet, introduce the research performed in their home institutions, and share their experience in science and academia. The conference welcomed 90 participants including students and scientists at early career to senior positions (Figure 1). After similar, smaller meetings held in 2015 in Germany (Bonn, Hannover, and Munich), this was the first supra-regional WiS conference, counting with a professional infra-structure, speed-networking opportunities and an online survey for quality control. Scientific and networking highlights of the conference are described below.

Renata Stripecke (CRC 738, Hannover): Opened the conference and explained the motivations of this meeting. The proportion of female science professors continues to remain significantly low (approximately 20% in Germany). With an increasing number of institutes striving to close the gender gap, now the female scientists are getting together “bottom-up” to discuss not only the numbers, but also the quality of their career perspectives. The main goal was to improve the awareness of female scientists regarding their responsibilities to “lean in” and to progress towards fulfilling careers, not give up. In addition, the meeting offered an opportunity for women to cross borders towards other institutions for scientific collaborations. The scientific thematic was focused on each speaker's research funded as Principal Investigators (PIs) by the DFG Collaborative Research Centers (CRCs) (Table 1).

Gene regulation, hematopoietic cells and inflammation

Claudia Waskow (CRC 655, Dresden): She presented her work on novel recipient mice for humanization using human hematopoietic stem cells (HSCs). Such mice are in urgent need to study human HSC biology and haematopoiesis in an in vivo environment, and to test personalized therapies. Her group developed three novel immune-deficient murine recipients that harbour a functionally impaired endogenous HSC compartment, and therefore, accept exogenous human donor HSCs in the absence of any conditioning therapy (BALB/c Rag2⁻ Il2rg⁻ Kit^Wv/Wv, NSG Kit^Wv/+, NSG Kit^W41/W41) 1. Even the transplantation of low numbers of human donor cells allows for robust, sustained, and serially transplantable engraftment of human HSCs. These mice are excellent tools to study the function of human HSCs and the lineage potential of human donor cells because of the robust engraftment of cells of the myeloid, erythroid lineage and megakaryocytes.

Jacqueline Mermoud (CRC-TRR 81, Marburg): Her talk focused on how mammalian genomes are regulated at the level of chromatin by modification of histone residues. Mouse embryonic stem cells (ESCs) are used as model system as they have an open, hyperdynamic and transcriptionally permissive chromatin environment. When ESCs differentiated, the levels of heterochromatin increased. SMARCAD1 was identified as a chromatin remodelling enzyme which was highly expressed in ESCs. SMARCAD1 depletion from somatic cells leads to global changes in histone modifications 2. Loss of SMARCAD1 function in ESCs resulted in a reduced growth rate and exit of the pluripotent state. Analysis of the SMARCAD1 protein complex revealed properties linked to ESCs function and pluripotency. These findings may have potential implications for the reprogramming of induced pluripotent stem cells.

Katrin Busch (CRC 873, Heidelberg): She described a novel fate mapping mouse model (Tie2^MCM/+RosaYFP) allowing inducible genetic labelling of the most primitive Tie2⁺ HSCs in the bone marrow in situ to quantify hematopoietic development from HSCs by limiting dilution analysis and data-driven modelling 3. In situ labelling data showed that steady-state haematopoiesis was driven by polyclonal participation of at least 1/3 of the HSC compartment in adult mice over time. However, the individual HSC contribution was low. These results revealed fundamental differences in terms of HSC diversity and contribution as observed in post-transplantation haematopoiesis and displayed important issues in particular concerning medical implications. Based on the knowledge of normal steady-state haematopoiesis, this mouse model allowed gaining insights into regulation and differentiation processes under perturbed conditions such as irradiation, immune depletion, infections, serial bleeding, G-CSF mobilization or cancer development.

Irmgard Förster (CRC 704, Bonn): Her group investigates the functional properties of the chemokine CCL17 in reporter and knockout mouse models. After demonstrating that CCL17 is an important mediator of allergic skin diseases, they showed that CCL17 not only mediated DC/T cell interactions but also enhanced the migration of DC towards CCR7 ligands. Recent work in cooperation with John Hamilton (Melbourne, Australia) identified GM-CSF and IRF4 as important inducers of CCL17, and demonstrated an essential role of CCL17 in the development of arthritic pain and inflammation of the joints 4. Together with Günter Mayer from the CRC704, they generated novel RNA-based aptamers specific for CCL17, and showed that they efficiently blocked the development of contact hypersensitivity in vivo. These new reagents may support the development of novel drugs for treatment of inflammatory diseases.

Nina Wettschureck (TRR128, Bad Nauheim): Recent results regarding the role of G protein-coupled receptors (GPCRs) in neuroinflammation were presented. Together with Markus Schwaninger (Lübeck, Germany) she showed that dimethyl fumarate, a drug recently approved for the treatment of multiple sclerosis, is mediated by GPCR HCA2, which negatively regulates neutrophil adhesion and migration 5. Furthermore, she presented first single-cell GPCR expression data in murine leukocytes during neuroinflammation. These data showed a remarkable degree of heterogeneity of GPCR expression. In addition, her work revealed functionally relevant subpopulations of immune cells with specific GPCR repertoires, which may provide a basis for selective pharmacological targeting.

Beate Sodeik (CRC 900, Hannover): Her group investigates the dynamics of herpes simplex virus (HSV) cell entry, replication and assembly in keratinocytes, neurons, immune cells, and murine infection models mimicking HSV diseases. Herpesviruses require many nuclear functions for viral transcription, replication, and capsid assembly, and therefore, depend on host factors that ensure active nuclear import and export of viral and host proteins. She presented novel fluorescence life cell imaging data showing that in epithelial cells and primary neurons different host importins were required for axonal capsid transport and targeting to the nuclear pores, where the viral genomes were uncoated and released into the nucleus for transcription and replication (Bialy, Anderson, Döhner & Sodeik, manuscript in preparation). These data revealed an unexpected intimate relationship between cytosolic microtubule cargo transport and cargo targeting to nuclear pores.

Advances in immunotherapy

Cécile Gouttefangeas (CRC 685, Tübingen): Two generations of anticancer vaccines were presented. In an early-phase study for prostate carcinoma, patients received peptides representing known T-cell epitopes from prostate-associated antigens, either alone or with one out of four immunomodulators. This approach was feasible and safe. Clinical responses (based on PSA serum levels and time-to-next therapy) were more frequent in patients who received TLR7 ligands as adjuvants, and tended to associate with broader anti-vaccine T cell responses. To increase clinical efficacy, the research Department has now established a platform for vaccine personalization; the approach integrates genomics, transcriptomics and HLA-ligandomics data for designing optimized tumour-specific vaccines for each patient. Encouraging results were obtained in a patient with advanced cholangiocarcinoma, who experienced a remarkably stable clinical course after receiving a personalized peptide cocktail 6.

Ulrike Köhl (CRC 738, Hannover): She summarized clinical studies using chimeric antigen receptor (CAR)-T cells for cancer treatment. Targeting of CD19⁺ haematological malignancies is an increasing field leading to promising results with improved survival of the patients. However, most tumour antigens are also expressed in healthy tissues with a high risk to evoke severe toxicity after CAR-T-cell infusion. Since autologous T cells cannot consistently be expanded ex vivo for all patients, alternative strategies are important, such as CAR-NK cells 7. Since NK cells have a significant shorter lifespan than T cells, off-tumour toxicity might be reduced. However, mature NK cells lack memory response and repeated cell infusions might be needed for durable anti-tumour effects, which is currently being investigated in first clinical trials. Finally, international efforts to optimize and harmonize the manufacturing and approval process of CAR effector cells were presented.

Angela Krackhardt (CRC 824, Munich): She presented a pipeline for identification of T-cell receptors (TCR) targeting diverse tumour-related antigens including neoantigens. Her group has also developed a novel imaging strategy to non-invasively track TCR-transgenic T cells. This Immuno-Pet approach makes use of a Zirconium-labelled antibody directly binding to the murinized constant beta domains of transgenic TCRs independently of their specificity 8. Application of a radiolabelled F(ab)₂ fragment allowed visualization of T-cell accumulation in the antigen-presenting tumour by PET-CT. Moreover, a heterogeneous distribution pattern was observed depending on the tumour rejection phase, which was validated by semi-quantitative immunohistochemistry analysis. This approach is now in progress for clinical translation.

Networking and career perspectives

Jasmin Döhling-Wölm (Karrierekunst): She presented a provocative talk “Might and Power of Career networks – The strategies of successful people in science, industry and politics”. Here, the audience was introduced to some aspects of effective networking, such as keeping in touch with key mentors and collaborators, and understanding the principles of “tit for tat”. This was followed by an interactive discussion with the audience on the different styles and stereotypes women and men may have for networking and for promoting their careers.

Julie Heinecke and Lana Semykina (EMBL): They organized the speed-networking session. Each participant had the opportunity to meet for 5 minutes with 10–12 others. This event was followed by dinner and drinks, allowing a rapid interaction between scientists from different institutions and career stages. It was one of the highlights of the conference, according to the post-meeting survey.

Gerlind Wallon (EMBO): She is EMBO deputy director and leads the EMBO's Women in Science activities. She discussed in detail the reasons for and against quotas in science and academia. Whereas the proportion of women is approx. 50% during university studies up to post-doctoral positions, only approx. 20% of the senior scientists in academia are female in Europe (https://ec.europa.eu/research/swafs/pdf/pub_gender_equality/she_figures_2015-final.pdf). Although mathematical models clearly demonstrated that quotas could accelerate reaching a better gender balance within higher positions, they are not well accepted in academia as they are regarded as thwarting the merit system and may add a stigma to women's advancement.  One of the chairs of the conference (Prof. Hans-Georg Rammensee) suggested that, instead of quotas, financial incentives to the institutions for recruitment of women in academia could lead to positive effects.

Ursula von Gliscynski (DFG): She is a Programme Director at the DFG's division for “Research Centres“. Her presentation emphasized the strong interest of the DFG to achieve gender equality as the underrepresentation of women scientists in higher academic positions is a significant loss of talent, compromising efficiency and excellence in education and research. Currently, only 10% of the coordinators of CRCs are female, a rate well below the proportion of female professorships in Germany. To promote gender equality, the DFG has set up a series of internal measures implementing a vice president responsible for equal opportunities, as well as increasing the representation of women in DFG statutory bodies and in the grant review process. Equality measures within DFG funding programs include: funds for career development of female scientists, financial support for family-friendly measures and scientists having young children as well as for gender awareness activities. After intense evaluation of research-oriented standards in gender equality in the years 2008–2013, the DFG has now put this topic as top on the agenda for the general assembly 2017, where decisions about the future strategies will be taken. A wide spectrum of further information on activities supporting career development and family can be found in the new DFG toolbox (www.instrumentenkasten.dfg.de).

Charlotte Esser (Leibniz Research Institute for Environmental Medicine, Düsseldorf): She leads the Commission of Equality and Gender Support of the DGfI, together with Johannes vom Berg (Zürich, Switzerland). The DGfI currently has 2400 members, 42% of which are female. The main emphasis of the DGfI Commission is to equally support young male and female scientists, in particular those having families, during the critical phase of the transition from PhD/postdoctoral work to setting up their own independent research group. The Commission promotes educational events and networking opportunities.

Summary and Conclusions

The WiS conference 2016 was an interdisciplinary event bringing complementary scientific topics together with networking sessions in an open and constructive atmosphere. Most noticeable was the unanimous feedback by conference participants appreciating the high scientific level of the conference, as well as the round table and speed networking sessions, which were highly informative and interactive. Plans to have further regular WiS conferences, to integrate more CRCs, and to expand to other European countries are in progress. These activities will complement already existing initiatives by the European Federation of Immunological Societies (EFIS) and the European Journal of Immunology (EJI) that promote the visibility and appreciation of women in immunology, i.e. the EFIS-EJI Ita Askonas Award 9 and the EFIS initiative to establish a comprehensive database of female investigators in Europe with expertise in immunology 10.