Robert Insall

Last updated

Professor

Robert Insall

FRSE
Born1965
London
CitizenshipU.K.
EducationBA (Hons) University of Cambridge, PhD Cambridge University, Post-doctoral training Johns Hopkins University
Scientific career
FieldsCell Biology, Systems Biology, Cancer Biology
Institutions University College London, University of Glasgow
Thesis A candidate receptor for DIF in Dictyostelium. (1990)
Doctoral advisor Rob Kay
Other academic advisors Peter N. Devreotes

Robert Insall is the professor of computational cell biology at University College London and the University of Glasgow. His work focuses on how eukaryotic cells move, and how they choose the direction in which they move. He is known for demonstrating that cells can spread in the body [1] [2] and find their way through mazes [3] [4] [5] by creating gradients of chemoattractants.

Contents

Career

Insall performed his PhD work at the MRC Laboratory of Molecular Biology, working with developmental biologist Rob Kay, and his post-doctoral training with Peter Devreotes at Johns Hopkins University. After holding positions at the MRC Laboratory for Molecular Cell Biology at University College London, the University of Birmingham and the University of Glasgow, he moved to University College London in 2023. [6] His laboratory is currently located in the Darwin Building in Bloomsbury. He was elected as a Fellow of the Royal Society of Edinburgh in 2014. [7]

Key scientific contributions

With Laura Machesky, he identified an important signaling pathway that controls the behavior of the actin cytoskeleton. [8] Insall later proposed that chemotaxis, the process by which cells move towards sources of nutrients or other chemoattractants, is not driven by signaling from the cell membrane but instead by influencing the rate or direction of the extension of pseudopodia, protrusions that the cell uses to move. [9] He later introduced the idea that instead of responding to pre-formed chemoattractant gradients, cells generate these gradients themselves by degrading the chemoattractant. [10] He showed that the spread of cancer cells in melanoma is driven by this mechanism, [1] [2] and that cells migrating through a maze can tell the difference between short arms of the maze and long arms because the chemoattractant in a short arm is degraded more rapidly, allowing them to avoid getting lost. [4] [3] [5]

Other activities

Insall is a frequent commentator on issues related to science policy, [11] [12] [13] [14] reproducibility, [15] and science publishing. [16] [17] He was chosen by secondary school students as the best communicator in the 2012 I'm a Scientist, Get me out of here! competition for cancer researchers. [18]

Family

Insall's father, Donald Insall, is a noted architect. His wife, Laura Machesky, FRSE, FMedSci is the Dunn Professor of Biochemistry at the University of Cambridge. [7] The two researchers frequently collaborate.

Related Research Articles

<span class="mw-page-title-main">Chemotaxis</span> Movement of an organism or entity in response to a chemical stimulus

Chemotaxis is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming toward the highest concentration of food molecules, or to flee from poisons. In multicellular organisms, chemotaxis is critical to early development and development as well as in normal function and health. In addition, it has been recognized that mechanisms that allow chemotaxis in animals can be subverted during cancer metastasis. The aberrant chemotaxis of leukocytes and lymphocytes also contribute to inflammatory diseases such as atherosclerosis, asthma, and arthritis. Sub-cellular components, such as the polarity patch generated by mating yeast, may also display chemotactic behavior.

Chemotropism is defined as the growth of organisms navigated by chemical stimulus from outside of the organism. It has been observed in bacteria, plants and fungi. A chemical gradient can influence the growth of the organism in a positive or negative way. Positive growth is characterized by growing towards a stimulus and negative growth is growing away from the stimulus.

<span class="mw-page-title-main">Phosphatidylinositol (3,4,5)-trisphosphate</span> Chemical compound

Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases' (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane.

Michael Samuel Neuberger FRS FMedSci was a British biochemist and immunologist.

<span class="mw-page-title-main">ACTR3</span> Mammalian protein found in Homo sapiens

Actin-related protein 3 is a protein that in humans is encoded by the ACTR3 gene.

<span class="mw-page-title-main">ACTR2</span> Mammalian protein found in Homo sapiens

Actin-related protein 2 is a protein that in humans is encoded by the ACTR2 gene.

<span class="mw-page-title-main">WASF2</span> Mammalian protein found in Homo sapiens

Wiskott–Aldrich syndrome protein family member 2 is a protein that in humans is encoded by the WASF2 gene.

<span class="mw-page-title-main">FZR1</span> Protein-coding gene in humans

Fizzy-related protein homolog, also known as hCDH1, is a protein that in humans is encoded by the FZR1 gene.

RhoV is a small signaling G protein, and is a member of the Rho family of GTPases. Chp was identified in 1998 as a GTPase interacting with the p21 activated kinase PAK2. RhoV/Chp delineates with RhoU/Wrch a Rho subclass related to Rac and Cdc42, which emerged in early multicellular organisms during evolution. RhoV/Chp depends on palmitoylation rather than prenylation for association with plasma and intracellular membranes. In Xenopus embryos, RhoV is encoded by a canonical Wnt response gene and is induced in the developing neural crest at specification. RhoV activity cooperates with the Snai1 (Snail) transcription factor for the subsequent induction of the pro-invasive transcription factors Snai2 (Slug), Sox9 or Twist.

Rif is a small signaling G protein, and is a member of the Rho family of GTPases. It is primarily active in the brain and plays a physiological role in the formation of neuronal dendritic spine. This process is regulated by FARP1, a type of activator for RhoA GTPases. Alternatively, Rif can induce the formation of actin stress fibers in epithelial cells, which is dependent on the activity levels of ROCK proteins since the absence of ROCK activity would mean Rif would be unable to stimulate the growth of stress fibers.

<span class="mw-page-title-main">Bacterial motility</span> Ability of bacteria to move independently using metabolic energy

Bacterial motility is the ability of bacteria to move independently using metabolic energy. Most motility mechanisms that evolved among bacteria also evolved in parallel among the archaea. Most rod-shaped bacteria can move using their own power, which allows colonization of new environments and discovery of new resources for survival. Bacterial movement depends not only on the characteristics of the medium, but also on the use of different appendages to propel. Swarming and swimming movements are both powered by rotating flagella. Whereas swarming is a multicellular 2D movement over a surface and requires the presence of surfactants, swimming is movement of individual cells in liquid environments.

<span class="mw-page-title-main">Gliding motility</span>

Gliding motility is a type of translocation used by microorganisms that is independent of propulsive structures such as flagella, pili, and fimbriae. Gliding allows microorganisms to travel along the surface of low aqueous films. The mechanisms of this motility are only partially known.

<span class="mw-page-title-main">Arp2/3 complex</span> Macromolecular complex

Arp2/3 complex is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton-containing eukaryotic cells. Two of its subunits, the Actin-Related Proteins ARP2 and ARP3, closely resemble the structure of monomeric actin and serve as nucleation sites for new actin filaments. The complex binds to the sides of existing ("mother") filaments and initiates growth of a new ("daughter") filament at a distinctive 70 degree angle from the mother. Branched actin networks are created as a result of this nucleation of new filaments. The regulation of rearrangements of the actin cytoskeleton is important for processes like cell locomotion, phagocytosis, and intracellular motility of lipid vesicles.

<span class="mw-page-title-main">Biomolecular gradient</span>

A Biomolecular Gradient is established by a difference in the concentration of molecules in a biological system such as individual cells, groups of cells, or an entire organism. A biomolecular gradient can exist intracellularly or extracellularly. The purposes of such gradients in biological systems vary, but include chemotaxis and functions in development. These types of gradients play a role in many different types of signaling as well as recently being implicated in cancer metastasis.

Laura Machesky FRSE FMedSci is a British-American cancer research scientist currently based in the University of Cambridge. Professor Machesky is the Sir William Dunn Professor of Biochemistry in the Department of Biochemistry, and the current president of the British Society for Cell Biology.

Peter N. Devreotes is an American scientist and the Isaac Morris & Lucille Elizabeth Hay Professor and former director of the department of cell biology, with joint appointments in the Center for Cell Dynamics and department of biological chemistry at the Johns Hopkins University School of Medicine. He also serves on the scientific advisory board of the Allen Institute for Cell Science. He is best known for his contribution in the field of eukaryotic chemotaxis, signal transduction, and phosphoinositides biology.

Elizabeth Gavis is an American biologist who is the Damon B. Pfeiffer Professor of Life Sciences, at Princeton University. Gavis served as the President of the North American Drosophila Board of Directors in 2011.

<span class="mw-page-title-main">Run-and-tumble motion</span> Type of bacterial motion

Run-and-tumble motion is a movement pattern exhibited by certain bacteria and other microscopic agents. It consists of an alternating sequence of "runs" and "tumbles": during a run, the agent propels itself in a fixed direction, and during a tumble, it remains stationary while it reorients itself in preparation for the next run.

Ahna Renee Skop is an American geneticist, artist, and a professor at the University of Wisconsin–Madison. She is known for her research on the mechanisms underlying asymmetric cell division, particularly the importance of the midbody in this process.

<span class="mw-page-title-main">Adventurous motility</span>

Adventurous motility is as a type of gliding motility; unlike most motility mechanisms, adventurous motility does not involve a flagellum. Gliding motility usually involves swarms of bacteria; however, adventurous motility is practiced by individual cells. This gliding is hypothesized to occur via assembly of a type IV secretion system and the extrusion of a polysaccharide slime, or by use of a series of adhesion complexes. The majority of research on adventurous motility has focused on the species, Myxococcus xanthus. The earliest of this research is attributed to Jonathan Hodgkin and Dale Kaiser.

References

  1. 1 2 Muinonen-Martin, Andrew J.; Susanto, Olivia; Zhang, Qifeng; Smethurst, Elizabeth; Faller, William J.; Veltman, Douwe M.; Kalna, Gabriela; Lindsay, Colin; Bennett, Dorothy C.; Sansom, Owen J.; Herd, Robert (2014). "Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal". PLOS Biology. 12 (10): e1001966. doi: 10.1371/journal.pbio.1001966 . ISSN   1545-7885. PMC   4196730 . PMID   25313567.
  2. 1 2 Reid, Rob (14 October 2014). "Scottish scientists discover new clues to stopping spread of skin cancer cells around the body". Daily Record. Retrieved 17 May 2021.
  3. 1 2 Tweedy, Luke; Thomason, Peter A.; Paschke, Peggy I.; Martin, Kirsty; Machesky, Laura M.; Zagnoni, Michele; Insall, Robert H. (28 August 2020). "Seeing around corners: Cells solve mazes and respond at a distance using attractant breakdown". Science. 369 (6507): eaay9792. doi:10.1126/science.aay9792. ISSN   1095-9203. PMID   32855311. S2CID   221342551.
  4. 1 2 Klein, Alice. "Watch cells sniff their way around the maze from Hampton Court Palace". New Scientist. Retrieved 16 May 2021.
  5. 1 2 Brandon Specktor - Senior Writer 27 August 2020 (27 August 2020). "Cells solved Henry VIII's infamous hedge maze by 'seeing around corners,' video shows". livescience.com. Retrieved 17 May 2021.{{cite web}}: CS1 maint: numeric names: authors list (link)
  6. ↑ Beatson Institute. "Prof Robert Insall FRSE - Cell Migration and Chemotaxis | Invasion and Metastasis | The Beatson Institute Research Groups | Research". www.beatson.gla.ac.uk. Retrieved 17 May 2021.
  7. 1 2 "Couple have become fellows". Glasgow Times. Retrieved 17 May 2021.
  8. ↑ Machesky, L. M.; Insall, R. H. (1998). "Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex". Current Biology. 8 (25): 1347–1356. doi: 10.1016/s0960-9822(98)00015-3 . ISSN   0960-9822. PMID   9889097. S2CID   16661755.
  9. ↑ Insall, Robert H. (2010). "Understanding eukaryotic chemotaxis: a pseudopod-centred view". Nature Reviews. Molecular Cell Biology. 11 (6): 453–458. doi:10.1038/nrm2905. ISSN   1471-0080. PMID   20445546. S2CID   31476082.
  10. ↑ Tweedy, Luke; Knecht, David A.; Mackay, Gillian M.; Insall, Robert H. (2016). "Self-Generated Chemoattractant Gradients: Attractant Depletion Extends the Range and Robustness of Chemotaxis". PLOS Biology. 14 (3): e1002404. doi: 10.1371/journal.pbio.1002404 . ISSN   1545-7885. PMC   4794234 . PMID   26981861.
  11. ↑ Insall, Robert (2011). "Career postdocs increase scrap heap". Nature. 471 (7340): 578. Bibcode:2011Natur.471..578I. doi: 10.1038/471578e . ISSN   1476-4687. PMID   21455160.
  12. ↑ Insall, Robert (8 April 1999). "Cynicism and credulity". Current Biology. 9 (7): R231. doi: 10.1016/S0960-9822(99)80147-X . ISSN   0960-9822. PMID   10209127. S2CID   43192942.
  13. ↑ Insall, Robert (1 April 2000). "Too much of a good thing?". Current Biology. 10 (7): R253. doi: 10.1016/S0960-9822(00)00409-7 . ISSN   0960-9822. PMID   10753757. S2CID   935794.
  14. ↑ Insall, Robert (1 November 1997). "The right stuff". Current Biology. 7 (11): R665. doi: 10.1016/S0960-9822(06)00345-9 . ISSN   0960-9822. PMID   9382817.
  15. ↑ Siebert, Sabina; Machesky, Laura M.; Insall, Robert H. (14 September 2015). "Overflow in science and its implications for trust". eLife. 4. doi: 10.7554/eLife.10825 . ISSN   2050-084X. PMC   4563216 . PMID   26365552.
  16. ↑ Insall, Robert (2003). "Impact factors: target the funding bodies". Nature. 423 (6940): 585. Bibcode:2003Natur.423..585I. doi: 10.1038/423585b . ISSN   1476-4687. PMID   12789312.
  17. ↑ Insall, Robert (4 March 2003). "Robert Insall". Current Biology. 13 (5): R167–R168. doi: 10.1016/S0960-9822(03)00112-X . ISSN   0960-9822. PMID   12620201. S2CID   5302620.
  18. ↑ "Beatson 'celeb' scientist is UK winner for kids". Glasgow Times. Retrieved 16 May 2021.
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