The goal of our work is to understand the fundamental mechanisms controlling how cells migrate, deposit extracellular matrix, and remodel their environment. These behaviours are critical for normal embryonic development and pathologies such as tissue fibrosis and cancer metastasis. Our lab exploits both in vivo and in vitro model systems along with time-lapse imaging and computer vision approaches to understand both the genetics and the dynamics of these processes.
Lab members
- Leonel Cardozo De Menezes E Souza (PhD student)
- Angus Nichols (PhD student)
- David Salvador Garcia (Postdoc)
- Stefania Marcotti (Postdoc)
- Besaiz Sanchez Sanchez (Postdoc)
- Maria Carmen Diaz de la Loza (Technician)
People
Research Associate/ BioImage Analyst
Research Associate
Professor
Projects
Regulation of cell motility
Cell migration is critical for embryonic development and tissue repair and often goes awry during disease processes such as cancer. Despite this clinical significance, most of our knowledge surrounding how cells move stems from in vitro assays of limited physiological relevance. To begin to extrapolate some of our in vitro understanding of cell motility to an in vivo scenario, we are exploiting the embryonic developmental dispersal of Drosophila (fruit fly) macrophages (hemocytes). Much like human macrophages, these cells are crucial for innate immunity and are necessary for responses to infection and tissue damage. We have developed a number of microscopy techniques that allow us to image these cells migrating in vivo, during both wound responses and embryogenesis, at a spatial and temporal resolution approaching what can be achieved from cells in culture. This attribute, along with the genetic tractability of flies, enables us to examine the genes and cytoskeletal responses driving migratory processes within a living animal. This system has allowed us to elucidate the intracellular cytoskeletal dynamics controlling how cells move and coordinate the migratory process, along with the extracellular cues driving migration during development and tissue repair. We are also extrapolating this knowledge to other cell types and model systems with the goal of highlighting fundamental mechanisms controlling cell motility.
Extracellular matrix formation and function
Cells and tissues are surrounded by a complex extracellular matrix (ECM), which consists of numerous interconnected polymer networks containing components such as collagen. The lab takes advantage of both in vivo and in vitro model systems to understand how the ECM is regulated during both embryonic development and tissue fibrosis. We are currently exploiting our capacity to live image and genetically dissect ECM component polymerisation and function during Drosophila development. This work has revealed that the ECM is highly dynamic during embryogenesis and undergoes constant remodelling and turnover, which is essential for tissue formation and maintenance. We are currently using this system to understand critical factors controlling de novo ECM formation and homeostasis. We are also analysing the physiological effects of targeted mutations in specific ECM components, many with disease relevance of unclear aetiology, to understand the assembly of this complex polymer network. We have also started to use our expertise in ECM cell biology to examine the cellular changes that drive the remodelling of the matrix during scarring and fibrotic pathologies. During scarring the ECM undergoes a dramatic change in architecture, which leads to an alteration in the mechanical properties – and ultimately function – of the tissue. Fibroblasts isolated from several fibrotic skin pathologies reveals that these cells maintain a unique capacity to create a highly bundled ECM in culture and we are currently dissecting the cellular and molecular mechanisms controlling this process.
Publications
News
Advanced microscopy study reveals molecular details of tight control of cell migration
New research provides novel insights with potentially important implications for our understanding of Nance-Horan Syndrome and cancer metastasis.
Methods and protocols
Laser ablation of Drosophila epithelia- to study genetic wound response.
Live imaging using standard widefield or confocal microscopy - in vivo chemotaxis assay- as a model to identify, in vivo, the genes responsible for cell migration.
People
Research Associate/ BioImage Analyst
Research Associate
Professor
Projects
Regulation of cell motility
Cell migration is critical for embryonic development and tissue repair and often goes awry during disease processes such as cancer. Despite this clinical significance, most of our knowledge surrounding how cells move stems from in vitro assays of limited physiological relevance. To begin to extrapolate some of our in vitro understanding of cell motility to an in vivo scenario, we are exploiting the embryonic developmental dispersal of Drosophila (fruit fly) macrophages (hemocytes). Much like human macrophages, these cells are crucial for innate immunity and are necessary for responses to infection and tissue damage. We have developed a number of microscopy techniques that allow us to image these cells migrating in vivo, during both wound responses and embryogenesis, at a spatial and temporal resolution approaching what can be achieved from cells in culture. This attribute, along with the genetic tractability of flies, enables us to examine the genes and cytoskeletal responses driving migratory processes within a living animal. This system has allowed us to elucidate the intracellular cytoskeletal dynamics controlling how cells move and coordinate the migratory process, along with the extracellular cues driving migration during development and tissue repair. We are also extrapolating this knowledge to other cell types and model systems with the goal of highlighting fundamental mechanisms controlling cell motility.
Extracellular matrix formation and function
Cells and tissues are surrounded by a complex extracellular matrix (ECM), which consists of numerous interconnected polymer networks containing components such as collagen. The lab takes advantage of both in vivo and in vitro model systems to understand how the ECM is regulated during both embryonic development and tissue fibrosis. We are currently exploiting our capacity to live image and genetically dissect ECM component polymerisation and function during Drosophila development. This work has revealed that the ECM is highly dynamic during embryogenesis and undergoes constant remodelling and turnover, which is essential for tissue formation and maintenance. We are currently using this system to understand critical factors controlling de novo ECM formation and homeostasis. We are also analysing the physiological effects of targeted mutations in specific ECM components, many with disease relevance of unclear aetiology, to understand the assembly of this complex polymer network. We have also started to use our expertise in ECM cell biology to examine the cellular changes that drive the remodelling of the matrix during scarring and fibrotic pathologies. During scarring the ECM undergoes a dramatic change in architecture, which leads to an alteration in the mechanical properties – and ultimately function – of the tissue. Fibroblasts isolated from several fibrotic skin pathologies reveals that these cells maintain a unique capacity to create a highly bundled ECM in culture and we are currently dissecting the cellular and molecular mechanisms controlling this process.
Publications
News
Advanced microscopy study reveals molecular details of tight control of cell migration
New research provides novel insights with potentially important implications for our understanding of Nance-Horan Syndrome and cancer metastasis.
Methods and protocols
Laser ablation of Drosophila epithelia- to study genetic wound response.
Live imaging using standard widefield or confocal microscopy - in vivo chemotaxis assay- as a model to identify, in vivo, the genes responsible for cell migration.
Our Partners
Biotechnology & Biological Sciences Research Council
Group lead
Professor