Past Projects

Circulating leukocytes reach the tissue from blood through sequential stages, which includes rolling along the endothelium, firm arrest due to signalling events triggered by chemokines, subsequent integrin-dependent adhesion and endothelial transmigration. This project will address the ability of chemokines to control the polarisation, adhesion, margination and recruitment efficiency of leukocytes under flow conditions utilizing a previously developed proprietary multi-channel microfluidic-enabled platform. The aim of the project is to analyse the effect of distinctive chemokines known by their ability to influence blood lymphocyte and polymorphonuclear cell activation, on leukocyte polarity, adhesion and margination. In the course of the study we will test the hypothesis that chemokine-induced leukocyte polarization represents an essential stage in preparation of leukocytes for subsequent rolling and adhesion via changing of cell flow characteristics and subsequent preferential margination in the microcirculationvessels. Therefore, we will address the following specific tasks:(i) the effects of lymphocyte and neutrophil-specific chemokines on lymphocyte and polymorphonuclear morphology before the exposure to the flow conditions, (ii) the influence of these chemokines on leukocyte adhesion under condition imitating physiological flow and (iii) we will also investigate chemokine dependant changes in cell polarity, recruitment and margination under flow sheer stress conditions. As a result of the study, we will provide new fundamental information characterizing the multifactorial leukocyte navigation relevant to normal and inflammatory conditions and generate a basis for new diagnostic and therapeutic approaches.

Professor Yuri Volkov

We combine state-of-the-art techniques, methodologies, skills and instrumentation from several scientific arenas to create discipline-independent platforms to address key questions in nanotoxicology. Thus, we identify the routes via which nanoparticles enter and accumulate in living organisms, and connect this to representative cell-nanoparticle systems. Then using the most advanced methods of nanoparticle properties (in physiological conditions) to the mechanism via which they interact with, and disrupt, cellular processes. We establish means and protocols via which every step of the program will be controlled, eliminating the factors that currently cause irreproducibilities. We establish means and protocols via which every step of the program will be controlled, eliminating the factors that currently cause irreproducibilities. We emphasize novel unbiased assessments of intra-and inter-cellular processes after exposure to nanoparticles, enabling us to explore known, and unknown, processes. Key companies, large and small from several end-user groups, that are currently facing the challenge of applying nanotechnology in their products are built into the grogram in a substantial manner, and other key stake-holders are also incorporated into the overall consortium via the Advisory Board. This will ensure maximum uptake of the knowledge generated by NanoInteract, and enable development of standards for nanoparticle risk assessment.

Professor Yuri Volkov

An important step in the inflammatory response is the recruitment of leukocytes into tissues through the endothelial cells which line blood vessels. Transendothelial migration (TEM) is the result of a multistep cascade in which chemoattractant gradients mediate the migration of leukocytes through the endothelial wall and into the underlying tissue. The leukocyte transendothelial migration is a small part of the processes that comprises the immune system. However cell migration through the endothelium plays a role in the progression of diverse diseases, such as cancer metastasis and atherosclerosis, or physiological processes, such as embryonic morphogenesis and wound healing. It is necessary to understand the mechanisms of this migration in order to establish, through research, how to support, supplement and improve its function.

Consequently there are numerous in vitro assays which attempt to mimic chemotactic gradients. The majority of these assays have limitations as they take place in the absence of flow with no precise control over the concentration of the chemokine gradient. However in recent times the design of the standard chemotaxis assays has been reconsidered in order to incorporate modern microfluidic platforms, computer controlled flow devices and cell tracking software. Assays under fluid flow which use biochips have provided data highlighting the importance of shear stress on cell attachment and migration towards a chemokine gradient. However, the in vivo environment is much more complex than that which is found in conventional cell assay chambers and 2-dimensional biochips. To reproduce realistic in vivo conditions, microfluidic biochips must present an environment capable of replicating the release of a chemokine gradient from tissue through the endothelium, such as occurs at sites of inflammation.

Professor Yuri Volkov and Professor Igor Shvets