Projects / Programmes
Experimental biophysics of complex systems and imaging in biomedicine
January 1, 2019
- December 31, 2027
| Code |
Science |
Field |
Subfield |
| 1.02.07 |
Natural sciences and mathematics |
Physics |
Biophysics |
| Code |
Science |
Field |
| B002 |
Biomedical sciences |
Biophysics |
| Code |
Science |
Field |
| 1.03 |
Natural Sciences |
Physical sciences |
physical interactions, tissue barriers, nanomaterial, molecular mechanisms, in vitro models, advanced super-resolution imaging, magnetic resonance microscopy, novel diagnostic modalities, new STED probes
Data for the last 5 years (citations for the last 10 years) on
April 24, 2024;
A3 for period
2018-2022
| Database |
Linked records |
Citations |
Pure citations |
Average pure citations |
| WoS |
603 |
10,474 |
8,591 |
14.25 |
| Scopus |
631 |
11,484 |
9,517 |
15.08 |
Researchers (29)
Organisations (2)
Abstract
The rapid development of new nanomaterials, thin films and drugs in the last decades poses enormous challenge to safety testing and regulation due to inadequate methodology, which can be improved by recently developed biophysical approaches. Many material-associated health risks have been identified (Science 2017 355:342), but many of the basic molecular mechanisms remain unresolved (Arch. Toxicol. 2016 90:1769). After gene expression has been found to be substantially different between human and mouse (Nature 2014 515:355), explaining the failure of 95% of the drug tests during clinical trials (Proc. Natl. Acad. Sci. 2013 110: 3507), animal in vivo testing is phasing out and novel in vitro and in silico models are urgently searched for (Science 2010 328:1662, Nanomed. 2016 11:2457). Our recent discovery of nanomaterial-associated interaction-driven molecular events provides the tools potent of explaining what the cell signalling paradigm cannot explain.
With the recently introduced super-resolution microscopic tools in our labs, P1-0060 is going to develop new super-resolution-compatible functional tissue barrier models to explore the material-exposure-associated interaction-driven molecular events by combining and upgrading advanced optical (nonlinear, super-resolution and spectrally-resolved lifetime) and magnetic-resonance microscopies. The potential of our methodological arsenal and expertise will further drive development of novel diagnostic modalities for future diagnostic/theranostic technologies and new didactical approaches aimed at improving the quality of learning and problem solving in natural sciences.
Our research aims at clarifying the connections between molecular events within tissue barriers and adverse outcome pathways by biophysical concepts, affecting the general perception of the nanohazard as well as boosting the entire single-cell science field. With design and synthesis of new photo-stable and more specific probes we expect to further increase the applicability of the super-resolution live imaging and its application to the live tissue models. By coupling the detection of the spectral and lifetime information with advanced sampling concepts we want to make nondestructive characterization of tissues much more powerful tool, attractive to both Slovenian and international industry of medical devices.
By intensive PhD training programs and strong involvement in high education, we want to contribute to an increased level of expertise of young researchers and students of natural sciences. Many challenges and results are advertised through our social network profiles such as @StrancarLab to improve the public perception of the physics, biophysics, technology and life sciences in general.
Significance for science
Shifting the paradigm - new causal connections between molecular events
Molecular biology has evolved into mighty paradigm, offering almost perfect insight into the cellular signaling often leading to overwhelming complexity with little predictive power. However, in the perspective of the lung exposure to nanomaterial this paradigm fails to describe the initiating events and their connections to the subsequent cellular response such as local inflammation. Physical experimental and simulation tools, however, push the understanding forward by indicating that the barrier response might evolve due to purely interaction–driven phenomena. The results of the proposed scientific exploration might therefore shift the existing paradigm of cellular signaling by making the physical pathways at least equally relevant.
Development of 3-D tissue barriers to explore molecular mechanisms and the interactions live
Development of 3D tissue models, the so called in vitro models, organoids or organ-on-a-chip, has been recognized in January 2018 issue of the Nature Methods journal as the most important trend of method development to study human biology and disease development replacing less relevant in vivo animal models. Currently, the leading institution in this field is Harward’s Wyss Institute with its “Human-On-Chip”, which perfectly mimics the lung’s real immune cell migration over the air-blood barrier model, but, for example, fails to reflect the nanoparticle-associated interactions and events. Thus, fully functional barrier systems with an ability to explore and monitor the supramolecular structures’ changes in live with the resolution of 30 nm can boost at least entire single-cell science field, in particular understanding of connections between molecular events and systemic-like responses. With that ability, if proven, it can gain unprecedently large interest within drug-development field, boosting understanding of the function of these very important interface of our body and contributing to better drug delivery across the air-blood and olfactory barrier.
Pushing the super-resolution live STED imaging to explore the tissue models’ response
Seeing supramolecular structures in complex tissue samples has been restricted for a long time to electron microscopy imaging methods and limited only to fixed slices of the dead tissue. Recently developments of the super-resolution techniques like STED gave us possibility to see those structures under physiological conditions for the first time, facing wide spectrum of scientific challenges. For those to meet, first super-resolution imaging needs an improved point-spread-function suppression, which can be solved by using multi-photon excitation together with STED. Implementation of the latter is still far from being straightforward, let alone further enhancement by spectral & lifetime information. Together with design and synthesis of new superiorly photo-stable and significantly more specific probes can dramatically increase the applicability of the super-resolution live imaging and its application on the live tissue models. Not least, live STED (continuous) imaging is now hardly applicable due to substantial photobleaching.
Significance for the country
New tissue models to replace less relevant and cost-ineffective animal testing
It is expected, that development of new tissue models can directly affect pharmacology by improving the drug development cycles, 95% of which now fail in clinical phase due to differences in gene expressions between human and animal models. In addition, the toxicology and immunology fields will change as well replacing currently mandatory but questionable animal testing. The list of benefits will include reduction of the testing costs and, not to be overlooked, the ethical aspects of reduced animal experimentation.
New diagnostic modalities to increase diagnostic power
Currently, medical diagnostics seems to be decoupled from the therapeutic procedures, with the rationale behind originating in the incompleteness of the information despite the apparent complexity of the diagnostic methods, and in the associated inability of the operator to use these diagnostic methods in real time. Our activities aim at coupling the extraction of the spectral / lifetime information and advanced sampling concepts making nondestructive characterization of tissues, especially in ophthalmology, much more powerful tool. Based on the experience of the very recent development of the new diagnostic concept able to detect eye blood vessel pathology that trigger most of the (age-related) retinal pathologies, we expect to make more significant breakthroughs in the future. We will work on nonlinear-excitation based detection for enhanced optical sectioning in living tissues, application of programmable optical elements such as spatial light modulator in diagnostics to correct for optical error in optically dense tissues and to allow smart sampling in 3D. Finally, we want to couple these approaches to gated spectral-lifetime analysis to identify the cell changes that can later on lead to fatal tissue pathologies, which has already been attracted industrial partners .
Impact on health care sector
By development of tissue models and diagnostic technologies, P1-0060 directly influence the health care sector. In first place, by unravelling and informing both the general public as well as healthcare professionals about the causal pathway between the new materials / drugs and the disease development we contribute to awareness of adverse outcome pathways and symptom identification. In second place, by developing new diagnostics concepts we directly support both Slovenian and international industry of medical laser devices.
Impact on human resource development
P1-0060 group members are heavily involved in PhD training and high education by coordinating many courses at different Bologna level contributing to an increased level of expertise of young researchers and students of natural sciences. To advertise the physics, biophysics, technology and life sciences we edit the national journal paper for young mathematicians, physicists, astronomers and computers, while all together organize events for young students such as Days of Biophysics and press conferences to influence general perception of science in society. For the later, we also present the latest research on TV and in the quality daily journals. Within smart specialization, strategy and its Strategical development industrial partnership Factories of the future we coordinate the Photonic technology domain to foster knowledge transfer between the researchers of academia and those from industrial R&D groups.
Impact on promotion of country and access to foreign knowledge
By strong involvement in international projects / consortia and by attracting foreign PhD students, postdocs and already established researchers to our laboratories, we also promote Slovenia abroad; advertise our infrastructure and competences, and finally foster access to foreign knowledge at the same time.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
Interim report
