Research Fellow in Brain Vascular Biology and Brain Cancer Biology

Job title:

Research Fellow in Brain Vascular Biology and Brain Cancer Biology

Company

UCL

Job description

About UsThe UCL Cancer Institute is a £40 million investment in central London based at University College London (UCL), one of the world’s top universities and a founding member of the Francis Crick Institute. The Institute draws together over 400 scientists working together to develop world-class basic and translational cancer researchInformation about the UCL Cancer Institute can be found on our website https://www.ucl.ac.uk/cancer/The Group of CNS Angiogenesis and Neurovascular Link / Brain Vasculature and Perivascular Niche headed by neurosurgeon-neuroscientist Associate Professor Dr Thomas Wälchli is one of the laboratories of the University College London (UCL) Cancer Institute in the Department of Oncology of the University College London (UCL).Brain Vascular Biology and Brain Cancer Biology | UCL Cancer Institute – UCL – University College LondonThe overarching vision of the research of Associate Professor Dr Thomas Wälchli, MD-PhD, FMH neurosurgery is to understand how the brain vasculature is regulated during brain development, in the adult healthy brain, and in various vascular-dependent brain diseases such as brain tumours and brain vascular malformations.Background of the ProjectThe Central Nervous System (CNS) critically relies on the formation and proper function of its vasculature during development, adult homeostasis and disease, and cerebrovascular disease is a leading cause of death worldwide (Wälchli et al., Nature , 2024 ( https://www.nature.com/articles/s41586-024-07493-y ; https://www.nature.com/articles/d41586-024-02284-x ), Wälchli et al., Nat Rev Neurosci , 2023 ( https://www.nature.com/articles/s41583-023-00684-y ), Wälchli et al., Neuron , 2015 ( https://pubmed.ncbi.nlm.nih.gov/26182414/ )).Angiogenesis – the formation of new blood vessels – is highly active during embryonic and postnatal brain development (Wälchli et al., Proc Natl Acad Sci USA , 2013 ( https://www.pnas.org/doi/abs/10.1073/pnas.1216203110 ), Wälchli et al., Nat Protoc , 2015 ( https://www.nature.com/articles/nprot.2015.002 ); Wälchli et al., J Cereb Blood Flow Metab , 2017 ( https://pubmed.ncbi.nlm.nih.gov/27927704/ ); Wälchli et al., Nat Protoc , 2021 (https://www.nature.com/articles/s41596-021-00587-1); Wälchli et al., Arterioscler Thromb Vasc Biol , 2022 ( https://pubmed.ncbi.nlm.nih.gov/35196110/ )), enters almost complete quiescence in the healthy adult brain and is reactivated in vascular-dependent brain pathologies such as brain tumours and brain vascular malformations (Schwab et al…Wälchli, JCI Insight , 2023 ( https://insight.jci.org/articles/view/143071 ); Wälchli et al., Nature , 2024 ( https://www.nature.com/articles/s41586-024-07493-y ; https://www.nature.com/articles/d41586-024-02284-x ), Wälchli et al., Nat Rev Neurosci , 2023 ( https://www.nature.com/articles/s41583-023-00684-y )).Despite major advances in the understanding of the cellular and molecular mechanisms driving angiogenesis in peripheral tissues, developmental signalling pathways orchestrating angiogenic processes in the healthy and the diseased CNS remain incompletely understood.We recently performed scRNA-seq on approximately 600,000 freshly isolated ECs and PVCs from 47 fetuses and adult patients (Wälchli et al., Nature , 2024 ( https://www.nature.com/articles/s41586-024-07493-y ; associated Research Briefing in Nature https://www.nature.com/articles/d41586-024-02284-x ; associated Research Highlight in Nature Neuroscience https://www.nature.com/articles/s41593-024-01759-4 ; associated News & Views in Nature Reviews Cardiology https://www.nature.com/articles/s41569-024-01079-xThis unprecedented insight into EC and PVC heterogeneity and functional specialization of the human brain vasculature in development, health and disease at the single-cell level revealed the top differentially regulated pathways in both fetal and pathological brain ECs (including those in both low-grade and high-grade gliomas) as compared with healthy adult brain ECs.About the roleThe Group of Brain Vasculature and Perivascular Niche focuses on vascular growth and the development of blood vessels (angiogenesis) in the brain, including endothelial cells and perivascular cells of the neurovascular unit/perivascular niche, and on brain vascular heterogeneity in development, health and disease.The main aims are:

• to understand the cellular and molecular underpinnings that govern the growth of the developing, adult, and diseased human brain vasculature at single-cell resolution,
• to uncover the single-cell transcriptomic, genomic and epigenomic landscapes and spatial biology of the developing, adult and diseased human brain vasculature,
• to elucidate how developmental programs regulate vascular growth/angiogenesis in the human brain tumour vasculature (patho-fetal axis / onco-fetal axis),
• to unravel the onco-fetal programs of vascular growth/angiogenesis and immunosuppression/immunomodulation’
• to translate these fundamental insights about the onco-fetal axis in the human brain (tumour) vasculature into clinical settings with the ultimate goal to identify novel therapeutic strategies for human brain tumours (and for other vascular-dependent diseases such as human brain vascular malformations).

To tackle these fundamental challenges regarding the biology of the human brain vasculature in development, adulthood and disease, the group uses a variety of state-of-the-art technologies, including single-cell and spatial multi-omics, imaging mass cytometry, advanced imaging of human and mouse tissues, and innovative somatic mouse models. The focus of the team is on the most aggressive human brain tumours, notably primary brain tumours such as glial brain tumours (lower-grade gliomas, and the highly aggressive glioblastoma (GBMs)) as well as on secondary brain tumours such as brain metastases.The ultimate goal is to develop novel and conceptually different treatment strategies. Specific areas of focus are the developmental mechanisms (patho-fetal programs or onco-fetal programs) driving vascular growth in the human fetal brain and in human brain tumours, and how they are linked to immunosuppressive signals in the perivascular niche.The successful candidate is be expected to be a driving force of these highly novel, original and competitive projects, to produce independent and original research in this area, to develop and apply new concepts and to have a creative approach to problem solving.The post is funded for until 31 st December 2025 in the first instance .About youWe are exclusively looking for outstanding and highly motivated candidates.To tackle the above-mentioned high risk-high potential projects, candidates should demonstrate overwhelming enthusiasm for single-cell genomics, neuroscience, vascular biology, developmental biology, and cancer/tumor biology.

• A central component of the project will be the analysis, evaluation and interpretation of large-scale molecular (single-cell and spatial multi-omics) data using the latest bioinformatics/single-cell and spatial multi-omics tools and strategies. Therefore, excellent training, experience, knowledge, and enthusiasm in/for molecular- and cell biology, and single-cell and spatial multi-omics and computational biology/bioinformatics and biostatistics are required.
• Moreover, the candidate should be highly motivated and display a flexibility with regard to experimental (combination of various in vivo and in vitro experiments of human and mouse tissues) and organizational (the candidate will work at the University College London, in close collaboration with the Toronto Western Hospital, University Health Network and the University of Toronto) aspects. Therefore, we feel that only very dedicated, motivated, and talented candidates will be able to successfully work on the above-described, highly novel, original, translational and competitive projects with the potential to significantly enhance our knowledge on the biology of the human brain vasculature in development, adulthood, and disease.
• Finally, the candidate should have the ability and self-motivation to work both independently and as a team player and should demonstrate good communication skills.
• The successful candidate is be expected to be a driving force of these highly novel, original and competitive projects, to produce independent and original research in this area, to develop and apply new concepts and to have a creative approach to problem solving.
• Applicants who do not currently hold a PhD will not be considered for the position.
• Candidates who already did a first postdoc in one of the core expertise areas are highly encouraged to apply for this very competitive and attractive position.

The successful candidates :

• Have a PhD in bioinformatics/single-cell genomics/computer science (AI), neuroscience, vascular biology, developmental biology, cancer biology, immunology, biology/biomedicine, pharmacy, biomedical engineering, or related fields with ample research experience.
• Have strong skills in working in the fields of bioinformatics/single-cell genomics and/or spatial multi-omics, neuroscience, vascular biology, developmental biology, cancer biology and immunology and/or experience in biotech, intellectual protection, etc. are an extra-added value.
• Have a proven publication record with at least one first author publication in peer-reviewed international journals.
• Have experience in: (i) integrating single-cell and spatial multi-omics; (ii) computational programming in R, Python (and other common computer languages); (iii) competence/interest in analysing and integrating complex single-cell and spatial multi-omics- and clinical datasets are essential.
• Will be an ambitious researcher, motivated to apply his/her skills to diverse (medical) research projects and enjoy working in a collaborative, dynamic, vibrant and fast-paced team environment.
• Have excellent organizational and supervisory skills, you can work in a team as well as independently.
• Have a strong ability to multi-task, to meet timelines, to work accurately; you are stress-resistant.

What we offer and Our commitment to Equality, Diversity and InclusionAs well as the exciting opportunities this role presents we also offer some great benefits some of which are below:

• For rewards and benefits at UCL please visit:

https://www.ucl.ac.uk/work-at-ucl/reward-and-benefits You can read more about our commitment to Equality, Diversity and Inclusion here :

• https://www.ucl.ac.uk/equality-diversity-inclusion/

Expected salary

Location

London

Job date

Fri, 07 Feb 2025 23:54:01 GMT

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