Waldemar Kulig

Can we make biomaterials do more than just support tissue? What if they could deliver drugs exactly where they're needed, right from the surface? Research in biomaterials is rapidly evolving toward site-specific drug delivery, offering targeted therapeutic action while minimizing side effects. From orthopedic implants to contraceptive devices, implantable systems are being designed to release drugs precisely where and when they’re needed. However, challenges remain in integrating drug carriers directly onto material surfaces due to the diversity of biomaterials and their interaction with the body. As a result, only a few such systems are in clinical use today. Ongoing research focuses on functionalizing these surfaces to allow seamless embedding of bioactive molecule nanoparticles, paving the way for smarter, more effective therapeutic materials.

What if aging and disease were driven by a buildup of reactive molecules? Could understanding oxidative stress help us slow them down? Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), plays a central role in aging and many diseases — including cancer, diabetes, Alzheimer’s, and cystic fibrosis. While our cells have evolved both enzymatic and non-enzymatic defense systems to neutralize ROS, these defenses aren’t always enough. The imbalance between ROS production and antioxidant defenses leads to cellular damage that accumulates over time. In this project, we explore the molecular mechanisms behind oxidative stress at the cellular level, aiming to shed light on its role in age-related decline and disease progression.

How do cells sense their environment and decide how to respond? G protein-coupled receptors (GPCRs) are at the heart of this molecular communication. GPCRs form a vast and versatile family of cell surface receptors that detect external signals — ranging from light and odors to hormones and neurotransmitters — and convert them into specific cellular responses. These receptors are essential for many physiological processes, including vision, smell, taste, neural signaling, cardiovascular regulation, and reproduction. Unsurprisingly, GPCRs are the targets of 30–40% of all currently approved drugs. Despite their central role in biology and medicine, the precise molecular mechanisms by which GPCRs initiate and propagate signals remain incompletely understood. In this project, we investigate GPCR signal transduction at the atomistic level, using molecular simulations to uncover how structural changes in the receptor translate extracellular cues into intracellular action.

Every breath you take depends on an extraordinary biological interface: the pulmonary surfactant. But how does it actually work? Oxygen transport in the lungs begins in the alveoli — tiny air sacs where gas exchange occurs — and relies on the pulmonary surfactant (PSurf), a thin lipid-protein layer that lines the alveolar surface. This surfactant is essential not only for efficient oxygen diffusion into the bloodstream but also for preventing alveolar collapse during breathing. Despite its vital role, the molecular mechanisms by which PSurf supports oxygen transport remain poorly understood. Deficiency or malfunction of this system leads to life-threatening respiratory disorders such as neonatal and acute respiratory distress syndromes, cystic fibrosis, pneumonia, and bronchiolitis. In this project, we explore the physical and molecular principles that govern the function of pulmonary surfactant, aiming to uncover how this remarkable biological material makes breathing possible.

Proteins and lipids team up in complex ways that are essential for life, yet the details of their interaction remain a mystery. Cell membranes are dynamic structures where lipids and proteins closely interact to regulate key biological processes, from signaling and transport to membrane integrity and cellular communication. These protein-lipid interactions shape the membrane’s architecture and influence how cells respond to their environment. Despite their importance, the atomistic mechanisms driving these interactions are still not fully understood. Disruptions in protein-lipid interplay are linked to numerous diseases, including neurodegeneration and metabolic disorders. Our research aims to unravel the molecular details of how proteins and lipids cooperate within membranes, shedding light on the fundamental principles that govern cellular function and opening doors for novel therapeutic strategies.

Cutting-edge science demands cutting-edge tools — developing new computational methods is at the heart of breakthroughs. Innovative simulation techniques, including the development and refinement of molecular force fields, enable us to explore biological systems with unprecedented accuracy and realism. Traditional approaches often struggle to capture the complexity of biomolecular interactions and dynamics. By advancing force fields and other computational methods, we push the boundaries of molecular modeling and deepen our understanding of biological processes. These tools not only empower our research on membranes, proteins, and nanoparticles but also provide valuable resources for the broader scientific community, accelerating discoveries across biophysics and molecular biology.