Scientists seek to better understand biological differences in males and females, ultimately improving future precision healthcare approaches
By Jana Křížová, Fellow at Czech Academy of Sciences, Institute of Physiology and PostDoc at Institute of Physiology, CAS, Prague
As someone new to the field of sex differences, I realised that this meeting was not just a series of presentations - it represented a collective paradigm shift. The scientific community has shifted from merely describing phenotypic variations between males and females (sex differences) to the more important task of unlocking the exact genetic, hormonal, epigenetic, and environmental mechanisms that drive these differences.
The following are five ways the symposium introduced me to this new frontier:
1. Sex differences as a biological consequence of evolution
One of my first major insights at the symposium was that sex differences are not mere clinical complications or statistical noise to be disregarded; they are fundamental to evolutionary biology. Distinct evolutionary pressures have tailored the physiology of males and females in unique ways to optimise survival, adaptation, and reproduction, as we saw illustrated across an incredible diversity of evolutionary models. Elizabeth Rideout (University of British Columbia, Canada) highlighted mitochondrial adaptation, noting that protein synthesis levels are notably higher in female Drosophila. This shows how females adapt mitochondrial growth to meet the high energy needs of producing eggs and, in some species, caring for offspring over time.
Alexandra Milona (The Francis Crick Institute, UK) discussed organ plasticity, demonstrating that the mouse intestine expands during pregnancy and lactation to maximise nutrient absorption, but permanently retains an altered morphological and molecular baseline afterwards - a lifelong structural footprint of maternal evolutionary adaptation. Margarida Cardoso-Moreira (The Francis Crick Institute, UK) used Poeciliidae fish to study how placentas have evolved as fetal support systems.
2. Personalised medicine: pushing beyond the male baseline
For generations, medicine has operated under the assumption that treating patients based on their age, lifestyle, or clinical history was an adequate standard of care. Historically, clinical research has used males as the baseline. Personalised medicine can actively push research towards the specific molecular needs of all people. And we can unlock the majority of true clinical personalisation simply by integrating biological sex differences into healthcare.
The translational power of this approach was evident across several breakthroughs. For example, Colinda Scheele (KU Leuven University, Belgium) presented findings showing that timing chemotherapy according to a breast cancer patient's menstrual cycle can maximise drug efficacy and significantly improve survival rates. Taru Tukiainen (Institute for Molecular Medicine, Finland) demonstrated how large-scale human datasets enable us to understand the intersection of sex chromosomes, endocrine contexts, and life-history exposures in shaping human disease risk. Kristina Haase (EMBL Barcelona, Spain) presented impressive 3D vascularised in vitro tissue models of the placenta, cardiac inflammation, and breast cancer that take biological sex into account.
3. Identifying what makes a 'good talk' and finding new connections at a brand-new conference
Establishing a new conference comes with obvious challenges, such as connecting researchers from diverse fields, including immunology, cardiology, neurology, microbiology, tissue engineering, and many more. I realised that the most impactful speakers don't just present isolated data; they construct conceptual bridges, provide historical context, and describe the models they use as simply as possible. Several speakers focused on identifying the mechanisms of sex differences in health and disease, and the talks naturally became interconnected.
The opening keynote talk by Arthur Arnold (UCLA, USA) provided a historical overview of how scientific opinions on sex differences have evolved while clearly identifying the current bottlenecks, such as tracking hormone levels and gene expression regulation by 'dosage compensators'. Agnese Loda (Institute Imagine/Institut Pasteur, France) demonstrated how the Xist RNA regulates and silences gene expression from the X-chromosome. Claudia Keller Valsecchi (Biozentrum, University of Basel, Switzerland) built on this by showing how Xist recruits protein complexes to drive multilayered chromatin remodelling. Sarah Hoelzl (Technical University of Munich, Germany) demonstrated how certain genes manage to 'escape' X-chromosome inactivation and how their expression fluctuates and changes during ageing. And finally, Xiaohong Xu (Fudan University, China) identified the neural circuits that govern sex-specific behaviours in mice by dissecting the pathways affected by genetic factors versus those shaped by exposure to hormones during development.
4. The irreplaceable chemistry of face-to-face interaction
Although digital and virtual options have rightly expanded global access to science, a spontaneous chemistry occurs when people gather in the same room, which digital platforms simply cannot replicate. Casual breakthroughs happen while queuing for coffee, during informal debates in the corridors of the EMBL Advanced Training Centre, or while standing shoulder-to-shoulder in front of a poster board. The organisers incorporated this human element by introducing a 'Poster Sneak Peek' format, which allowed attendees to view more than 60 posters and facilitated face-to-face networking opportunities.
5. Intergenerational synergy: cultivating internal motivation
It was inspiring to observe researchers from diverse fields and at various stages of their careers interacting with one another, driven by a shared curiosity to understand the reasons behind the sex differences they observe in their daily work. The attendees shared an authentic curiosity to solve an understudied frontier of biology. Ultimately, this symposium made a case for taking a new look at some basic questions in evolution and considering how this factors into the future of medicine. Understanding sex-specific biology will be key to unlocking true personalised healthcare.
