Professor Tarvinder Dhanjal - Diamonds Funding Heart Rhythm Research

Dr Alexiane Decout - Lactobacillus Crispatus Surface Layer Proteins, Multifaceted Players of Women’s Health
Abstract: Preterm birth is the leading cause of death among children under the age of 5yrs. In 30% of cases, it is preceded by preterm prelabour rupture of the fetal membrane (PPROM). A risk indicator for PPROM is vaginal dysbiosis. Term pregnancy is associated with an optimal vaginal microbiota characterised by low diversity, with lactobacilli species constituting the vast majority of the bacteria therein. Conversely, a switch toward a more diverse microbiota containing opportunistic pathogenic species and a reduced proportion of lactobacilli is associated with increased risk of preterm birth. Inflammatory pathway activation associated with PPROM can be triggered by pro inflammatory stimuli such as TLR4 ligands. Yet, how the vaginal microbiota modulate the fetal immunological environment and thus PPROM risk is not fully understood.

Using clinical isolates of vaginal pathogens and commensals we identified that lactobacilli associated with term birth selectively interacted with anti-inflammatory innate immune receptors. A unique feature of lactobacilli surfaces is the presence of surface layer proteins (SLPs) forming a crystallin array. Removal of SLPs from the surface of L. crispatus restored a strong TLR2 activation, indicating that TLR2 ligands are present on L. crispatus, but are shielded by the S-layer proteins. These S-layer proteins interacted selectively with anti-inflammatory receptors such as DC-SIGN, were detected in the vaginal cervico-vaginal fluids and were associated with decreased maternal inflammation in L. crispatus dominated clinical samples. These data provide new insight into immunological mechanisms of microbial associated preterm birth and may offer new targets for novel preventive strategies.

Abstract: To meet physiological demands, the rhythm and strength of cardiac contractions continuously adapt across different time scales, guided by extracellular biochemical signals sensed via cell surface receptors. Increasingly, it is recognized that cellular responses are influenced not only by the molecular identity and concentration of these signals but also by the information encoded in the varying temporal patterns of the signals encountered by the cell. In this talk, I will discuss the theoretical challenges of studying cellular signaling in non-stationary environments and explore how these challenges can be addressed using concepts from dynamical systems, particularly those related to long transients and criticality. I propose that cardiac cells are significantly influenced by the temporal characteristics of incoming biochemical signals, such as (nor-)adrenaline, angiotensin II, and growth factors. By examining cardiac cells dynamic environments, we can gain a deeper understanding of contractile regulation and remodeling processes (including hypertrophy, apoptosis, and fibrosis) and identify new therapeutic concepts for cardiac arrhythmias and heart failure.

Biography: Following his undergraduate studies in medicine and philosophy at the University of Duesseldorf (Germany), Dr Koch received his PhD in cardiac cell biology from King's College London (UK) in 2021. His research mainly focuses on how cells coordinate their responses to biochemical signals from their environment and how these processes are disrupted in human disease, using a combination of experimental and theoretical approaches. Currently, Dr. Koch is a postdoctoral fellow in the Cellular Computations & Learning group at the Max Planck Institute for Neurobiology of Behavior (Bonn, Germany), where he applies concepts from non-linear dynamics and complex systems to develop new frameworks for understanding how biological systems—from cells to brains—process information and adapt to their surroundings.