Research

Our medical target areas include infection biology, neuroscience, and cancer. These areas are, however, likely to expand due to the expected wide applicability of nanotechnology.
Nanotechnology-platforms under investigation include nanoparticles, DNA nanotechnology and organic bioelectronics. In addition to this, platforms are brought to the center as collaborations are established with researchers at national and international academic settings.

 

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Stem Cell Engineering

Ana Teixeira

The stem cell microenvironment holds the balance between stem cell proliferation and differentiation, essential in embryonic development and organ homeostasis. Micro environmental cues include chemical signals originating from the extracellular matrix, from growth factors or through cell-cell communication. In addition, the physical nature of the microenvironment provides mechanical and topographical cues to cells. The proper integration of microenvironmentalcues with cell intrinsic genetic and epigenetic programs regulates stem cell state and fate. Increased knowledge of these processes can provide insights into developmental processes and has the potential to find applications in stem cell therapy and in cancer treatments targeting cancer stem cells.

The overarching goals of our research group are to:

  1. Gain understanding of the responses of stem cells and cancer stem cells to extracellular inputs using micro- and nanotechnologies to engineer the stem cell microenvironment.
  2. Identify opportunities for cancer therapy that target the cancer stem cell/microenvironment interface.
  3. Improve the outcomes of stem cell therapy by manipulating the stem cell microenvironment in vivo.

With a focus on the nervous system, we are presently engaged in addressing the following questions: CNS development: Do mechanical forces regulate cell-cell communication through Notch signaling? Mechanical properties of the microenvironment are increasingly being recognized as important stem cell signals. Indeed, recent work suggests that stem cells may be poised to respond to mechanical stimuli (Engler et al. 2006). In neural stem cell cultures, we have previously observed that soft substrates with elasticity similar to the elasticity of the brain, promote neuronal maturation and astrocytic differentiation (Teixeira et al. 2009).

Cell-cell communication though the Notch pathway is used repeatedly throughout development and in the adult to control stem cell lineage decisions in numerous tissues. Whether mechanical forces play a role in the activation of Notch signaling is a long-standing controversy in the field. The observation that functional endocytosis in the ligand expressing cell is required for Notch activation in the receptor expressing cell suggests that the process of formation of the endocytic vesicles creates a tension force between ligand and receptor. A potential coupling between

Notch signaling activation and mechanical stimuli to the cell is particularly interesting in the context of development, where morphogenetic movements can create tension forces between cells.

Mouse embryonic stem cells (line: Nes_lmx1a) subjected to dopaminergic differentiation in a biodegradable scaffold.

In addition, the striking control of stem cell fate choices by mechanical properties warrants a closer look at the link between the mechanical microenvironment and Notch signaling activation.

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Elucidating cell signaling dependence on ligand nanoscale clustering

Björn Högberg   Ana Teixeira

In many types of cell-cell signaling systems important for neuronal development, it is becoming clear that the spatial arrangement of the cell surface receptors influences the signal pathways of the cell. Consequently, by changing the spatial arrangement of the ligands, the receptor spatial organization is changing and thus influences the signaling. The labs of Högberg and Teixeira are investigating these systems by controlling the precise nanoscale architecture of the ligand clusters using DNA origami nanostructures and probing receptor activation using fluorescence microscopy.

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Phagocytes and infection

Mikael Rhen

Phagocyte movement is central facet in our immune defense. However, selected bacterial intracellular infections hijack phagocytes for systemic spread. As many bacterial virulence factors specifically interfere with actin polymerization, one could envision that such virulence factors also affect phagocyte movement. Nanoscale bio-electronic cell culture devices open exciting possibilities to dissect connections between the ability of selected model pathogens - such as Burholderia thailandensis, Mycobacterium bovis and Salmonella enterica - and their virulence factors to interfere with phagocyte motility and chemotactic responses. The development of such systems will be applicable for a number of research fields involved in phagocyte biology and cellular microbiology.

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Stem cells in CNS development

Ana Teixeira

With a focus on the nervous system, we are presently engaged in addressing the following questions: Do mechanical forces regulate cell-cell communication through Notch signaling? Mechanical properties of the microenvironment are increasingly being recognized as important stem cell signals. Indeed, recent work suggests that stem cells may be poised to respond to mechanical stimuli. In neural stem cell cultures, we have previously observed that soft substrates with elasticity similar to the elasticity of the brain, promote neuronal maturation and astrocytic differentiation.

Cell-cell communication though the Notch pathway is used repeatedly throughout development and in the adult to control stem cell lineage decisions in numerous tissues. Whether mechanical forces play a role in the activation of Notch signaling is a long-standing controversy in the field. The observation that functional endocytosis in the ligand expressing cell is required for Notch activation in the receptor expressing cell suggests that the process of formation of the endocytic vesicles creates a tension force between ligand and receptor. A potential coupling between Notch signaling activation and mechanical stimuli to the cell is particularly interesting in the context of development, where morphogenetic movements can create tension forces between cells. In addition, the striking control of stem cell fate choices by mechanical properties warrants a closer look at the link between the mechanical microenvironment and Notch signaling activation.

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Nanoparticles for neurological imaging/therapy

Andreas Nyström

Creating nanoparticles that can cross the blood-brain barrier (BBB) and deliver contrast or therapeutics to the brain is a challenging new project in the Nyström Group. We are just now initializing this effort using advanced polymer nanoparticles and are looking to hire a post doc with expertise in polymer preparation and drug delivery applications.

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