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“A sweet view on biomaterials engineering” & “Single-cell immune profiling in health and disease”

CMCB Postdoc Seminar

Date:29.11.2019, 16:00 - 17:00
Speaker: Maria T. Pisabarro, Gloria Ruiz-Gómez (Postdoc) & Ezio Bonifacio, Gloria Kraus (Predoc)
Location: CRTD, auditorium left

Abstract “A sweet view on biomaterials engineering”:

The molecular recognition of glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS) by a variety of proteins in the extracellular matrix (ECM) is crucial for physiological processes such as tissue hemostasis and repair, cell growth and cell-migration. Therefore, chemically modified GAG derivatives constitute relevant molecules for the engineering of innovative biomaterials with application in tissue regeneration. We investigate the molecular recognition properties of several defined sulfated oligohyaluronan (sHA) and CS derivatives toward a set of regulatory proteins of the extracellular matrix (i.e. interleukin 8 (IL-8), sclerostin and vascular endothelial growth factor (VEGF)) using computational approaches (i.e. docking, molecular dynamics and binding free energy calculations) in combination with experimental techniques (i.e. fluorescence polarization, surface plasmon resonance and isothermal titration calorimetry) [1-6]. We will present a selection of these studies showing how defined GAGs chemical substitutions affect binding to the target protein in terms of strength, site and mode [5-6]. We use the obtained information to rationally design GAGs with customized properties for the engineering of new biomaterials for skin and bone regeneration.

Abstract “Single-cell immune profiling in health and disease”:

Type I diabetes (T1D) is a chronic organ-specific disease, which is characterized by a deficiency in endogenous insulin production, and it arises as the result of autoreactive immune cell-mediated destruction of insulin-producing beta-cells in the pancreas. Beta-cell targeted autoimmunity is already underway before the appearance of symptoms, and it is thought to be triggered by a combination of genetic and environmental factors, giving rise to autoreactive cells. Autoreactive T cells are considered the main effectors of beta-cell destruction, and CD8+ T cells are the predominant T cell population and most abundant inflammatory cell type in insulitis. The main antigen recognition tool of T cells is T cell receptor (TCR) expressed on their plasma membrane. However, other immune cell types are also present in the pancreatic infiltrate and can contribute either directly (CD4+ T cells, NK cells, B cells) or indirectly (macrophages, dendritic cells) to beta-cell death. Using 10xGenomics, a single-cell RNA sequencing (scRNA-Seq) platform that allows for simultaneous epitope and transcriptome measurement, and reconstruction of TCRs/BCRs in a paired manner, I would to like identify memory CD8+ T cell TCRs and memory B cell BCRs that confer specificity for different antigens and T1D relevant antigen peptides in patients at risk or at onset of T1D. Using samples from early childhood, this knowledge can then be used to potentially pinpoint the initiating event(s) causing autoimmunity and help to understand underlying autoimmune mechanisms that lead to T1D development.


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