Uppsala University

Description of the legal entity:

Uppsala University (UU) is an international research university focused on the development of science and education with 45,000 students, 6,800 employees and a turnover of SEK 6,300 million. Department of Immunology, Genetics and Pathology (IGP) at UU hosts research groups working on Vascular Biology, Medical and Clinical Genetics, Immunology, Pathology and Tumor Biology. Parts of the organization are integrated with the departments of Clinical Genetics, Immunology and Pathology at Akademiska sjukhuset (Uppsala University Hospital).

Vascular Development Laboratory (www.makinenlab.com) headed by Dr. Mäkinen develops and utilizes genetic mouse models in combination with molecular and cell biological approaches (including advanced microscopy and flow cytometry, (single cell) RNA sequencing) to study mechanisms that regulate the morphogenesis and functional specialisation of the vasculature. The lab also investigates how regulators of developmental (lymph)angiogenesis impact on genetic human diseases such as lymphoedema and vascular malformations. Recently, the lab has used bulk and single-cell RNA sequencing to uncover organ-specific molecular identity of lymphatic endothelium in multiple tissues and different types of vessels, and generated new genetic tools for targeting of LEC subtypes.

As part of the proposed research, the key tasks of the team include determining the molecular identity of collecting lymphatic vessels of the adipose tissue in mice, and developing methods for their visualization in vivo, which lie within the core expertise of the lab.

Curriculum Vitae:

Assoc. Prof. Taija Mäkinen (Female): PI with expertise in (lymphatic) vascular biology, in particular generation and characterisation of mouse models for studying vascular development and disease. H-index = 44 (Scopus), selected awards: KAW Scholar 2019, ERC Consolidator grant 2015, EMBO Young Investigator 2010.

Dr. Simon Stritt (Male): post doc with experience in platelet and vascular biology, in vivo mouse models and single cell analysis. H-index = 7 (Scopus), awards: postdoctoral fellowships from the German Research Council and EMBO.

Post doc with previous experience in vascular biology will be hired to work full time on the project.

UU Main tasks in the project per WP

• WP2: UU is WP leader and implicated in Mouse and tissue architecture analysis (Task 2.1 and 2.2),

WP9 UU will contribute to dissemination and communication activities.

List of up to 5 relevant publications, and/or products, services (including widely-used datasets or software), or other achievements relevant to the  call content

• Frye M, Taddei A, et al…, Harvey N, Kiefer F, Makinen T. Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program. Nat Commun 9: 1511 (2018).
• Zhang Y, Ulvmar MH, Stanczuk L, Martinez-Corral I, Frye M, Alitalo, K, Makinen T. Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms. Nat Commun, 9: 1296 (2018).Mi
• Martinez-Corral I, Ulvmar MH, Stanczuk L, Tatin F, Kizhatil K, John SWM, Alitalo K, Ortega S, Makinen T. Non-venous origin of dermal lymphatic vasculature. Circ Res 116: 1649-1654 (2015).
• Stanczuk L, Martinez-Corral I, et al…, Alitalo K, Graupera M, Mäkinen T. cKit lineage hemogenic endothelium-derived cells contribute to mesenteric lymphatic vessels. Cell Rep 10: 1708-1721 (2015).
• Tatin F, Taddei A, Weston A, Fuchs E, Devenport D, Tissir F, Makinen T. Planar cell polarity protein Celsr1 regulates endothelial adherens junctions and directed cell rearrangements during lymphatic valve Dev Cell 15: 31-44 (2013).

List of up to 5 relevant previous projects or activities, connected to the subject of this proposal

• Wallenberg Scholar, Knut and Alice Wallenberg Foundation, 18 MSEK (2019-2024), PI
• MSCA-ITN PhD training programme A.Cure, 3.7 MEUR (2019-2023), co-PI (8 PIs)
• Multi-PI programme grant from Knut and Alice Wallenberg Foundation, 59.985 MSEK (2016-2020), co-PI (5 PIs)
• ERC Consolidator grant LYMPHORG, 368 MEUR (2015-2020), PI
• Swedish Research Council – Distinguished Young Researcher grant, 18 MSEK (2015-2020), PI

Infrastructure and/or major items of technical equipment

Animal care SPF facility (in vivo imaging systems for live whole-body luminescence imaging, near-infrared imaging, high frequency ultrasound); Bioimaging Facility (transmission electron microscopy, flow cytometry [Flowsight, FACSaria, LSR Fortessa, Melody], microscopy [widefield, confocal, 2-photon, lightsheet, SIM]); Proximity Ligation Assay Platform (analysis of protein-protein interactions using PLA); Genome Center (next generation sequencing, oligonucleotide microarrays for mRNA and miRNA). Through the national SciLifeLab facilities access to e.g. mass spectrometry, single cell genomics and proteomics and bioinformatic support. The laboratory has a dedicated (time-lapse) confocal microscope (Leica SP8).

Operational capacity

Fully operational