Seamus Martin (biochemist)

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Seamus J. Martin is an Irish molecular biologist and immunologist working at The Smurfit Institute of Genetics in Trinity College Dublin. Since 1999, he has held the Smurfit Chair of Medical Genetics at Trinity College Dublin, and his research focuses on the links between cell death, cell stress, and inflammation. Martin is known for his contributions to understanding the molecular control of the mode of regulated cell death known as apoptosis. Martin received the 'GlaxoSmithKline Award' of the Biochemical Society in 2006, [1] the British Science Association's 'Charles Darwin Award' in 2005, and The 'RDS-Irish Times Boyle Medal' in 2014, [2] for his work on deciphering the role of caspases in apoptosis. In 2006, he was elected to the Royal Irish Academy, [3] in 2009 he awarded EMBO Membership, [4] and in 2023 he was elected to the Academia Europaea. [5] His research work is widely cited and he received a European Research Council Advanced Research award in 2021. [6]

Contents

Martin is an author of the 11th, 12th, and 13th editions of the award-winning textbook, Essential Immunology, [7] and since 2014, he has served as Editor-in-Chief of The FEBS Journal (Cambridge, UK), an international life sciences academic journal.

Biography

Martin studied biology and chemistry as an undergraduate at The National University of Ireland, Maynooth (NUIM), followed by a PhD in Cell Biology working with Tom Cotter at Maynooth University. After completion of his PhD, he moved to the Dept. of Immunology at University College London (UK) to carry out a post-doctoral fellowship working on HIV immunopathology with internationally known immunologist Ivan Roitt, FRS.  Supported by a Wellcome Trust International Prize Fellowship, he then relocated to the La Jolla Institute for Immunology, University of California, San Diego, USA, to undertake a second post-doc with US Immunologist and National Academy Member Douglas R. Green. In 1999 Martin moved to the Dept. of Genetics, Trinity College Dublin, where he was appointed to the Smurfit Chair of Medical Genetics.

Scientific contributions

Martin's research focuses on the molecular mechanisms governing regulated cell death and inflammation. Initially working on the role of proteases in coordinating programmed cell death (apoptosis), he made contributions to our understanding of how caspases become activated during apoptosis, the order of caspase activation events in the intrinsic and extrinsic caspase activation cascades, and how caspases coordinate apoptosis through proteolysis of hundreds of substrate proteins. [8] More recently, his work has focused on how caspases coordinate inflammatory cascades downstream of death receptor engagement. In parallel to his work on caspases, he has also made contributions to our understanding of how neutrophil proteases promote inflammation through processing and activation of members of the extended IL-1 family and has championed the idea that IL-1 family members represent the canonical ‘damage-associated molecular patterns’ that promote inflammation upon release from necrotic cells [9]

While working with Doug Green at La Jolla, Martin pioneered annexin V labeling as a probe for apoptotic cells [10] which has become the ‘gold standard’ for the measurement of apoptosis. He also established a mammalian ‘cell-free’ system for the study of caspase activation pathways in mammals,[13][14] and continued this work upon establishing his own laboratory.[15][16][17][18] Martin's recent work has focused on exploring the links between cell death signals and inflammatory signaling cascades. His laboratory has published a series of studies demonstrating that essentially all initiators of programmed cell death can also promote inflammation[19][20][21] and his current research is focused upon understanding how chemotherapeutic drugs can frequently trigger inflammation that may be detrimental to killing cancer cells.[222]  

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Related Research Articles

<span class="mw-page-title-main">Apoptosis</span> Programmed cell death in multicellular organisms

Apoptosis is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses 50 to 70 billion cells each day due to apoptosis. For the average human child between 8 and 14 years old, each day the approximate loss is 20 to 30 billion cells.

<span class="mw-page-title-main">Caspase</span> Family of cysteine proteases

Caspases are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009, there are 12 confirmed caspases in humans and 10 in mice, carrying out a variety of cellular functions.

Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are infected with viruses or bacteria. Granzymes also kill bacteria and inhibit viral replication. In NK cells and T cells, granzymes are packaged in cytotoxic granules along with perforin. Granzymes can also be detected in the rough endoplasmic reticulum, golgi complex, and the trans-golgi reticulum. The contents of the cytotoxic granules function to permit entry of the granzymes into the target cell cytosol. The granules are released into an immune synapse formed with a target cell, where perforin mediates the delivery of the granzymes into endosomes in the target cell, and finally into the target cell cytosol. Granzymes are part of the serine esterase family. They are closely related to other immune serine proteases expressed by innate immune cells, such as neutrophil elastase and cathepsin G.

<span class="mw-page-title-main">Death effector domain</span> InterPro Domain

The death-effector domain (DED) is a protein interaction domain found only in eukaryotes that regulates a variety of cellular signalling pathways. The DED domain is found in inactive procaspases and proteins that regulate caspase activation in the apoptosis cascade such as FAS-associating death domain-containing protein (FADD). FADD recruits procaspase 8 and procaspase 10 into a death induced signaling complex (DISC). This recruitment is mediated by a homotypic interaction between the procaspase DED and a second DED that is death effector domain in an adaptor protein that is directly associated with activated TNF receptors. Complex formation allows proteolytic activation of procaspase into the active caspase form which results in the initiation of apoptosis. Structurally the DED domain are a subclass of protein motif known as the death fold and contains 6 alpha helices, that closely resemble the structure of the Death domain (DD).

<span class="mw-page-title-main">CARD (domain)</span> Interaction motifs found in a wide array of proteins

Caspase recruitment domains, or caspase activation and recruitment domains (CARDs), are interaction motifs found in a wide array of proteins, typically those involved in processes relating to inflammation and apoptosis. These domains mediate the formation of larger protein complexes via direct interactions between individual CARDs. CARDs are found on a strikingly wide range of proteins, including helicases, kinases, mitochondrial proteins, caspases, and other cytoplasmic factors.

Guy Salvesen is a South African-born biochemist, best known for his work in the field of apoptosis. His research focuses on proteases and their inhibitors in humans, with particular emphasis on the caspases of the apoptotic cell death pathway.

<span class="mw-page-title-main">FADD</span> Human protein and coding gene

FAS-associated death domain protein, also called MORT1, is encoded by the FADD gene on the 11q13.3 region of chromosome 11 in humans.

<span class="mw-page-title-main">Caspase-9</span> Enzyme found in humans

Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene. It is an initiator caspase, critical to the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist, such as Mus musculus and Pan troglodytes.

Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of various bacterial, viral, fungal and protozoan infections by removing intracellular replication niches and enhancing the host's defensive responses. Pyroptosis can take place in immune cells and is also reported to occur in keratinocytes and some epithelial cells.

Inhibitors of apoptosis are a group of proteins that mainly act on the intrinsic pathway that block programmed cell death, which can frequently lead to cancer or other effects for the cell if mutated or improperly regulated. Many of these inhibitors act to block caspases, a family of cysteine proteases that play an integral role in apoptosis. Some of these inhibitors include the Bcl-2 family, viral inhibitor crmA, and IAP's.

<span class="mw-page-title-main">XIAP</span> Protein-coding gene in the species Homo sapiens

X-linked inhibitor of apoptosis protein (XIAP), also known as inhibitor of apoptosis protein 3 (IAP3) and baculoviral IAP repeat-containing protein 4 (BIRC4), is a protein that stops apoptotic cell death. In humans, this protein (XIAP) is produced by a gene named XIAP gene located on the X chromosome.

<span class="mw-page-title-main">Caspase 3</span> Protein found in humans

Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.

<span class="mw-page-title-main">Caspase 6</span> Enzyme found in humans

Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene. CASP6 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis, early immune response and neurodegeneration in Huntington's and Alzheimer's disease.

<span class="mw-page-title-main">APAF1</span> Mammalian protein found in Homo sapiens

Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.

<span class="mw-page-title-main">NLRP1</span> Human protein-coding gene

NLRP1 encodes NACHT, LRR, FIIND, CARD domain and PYD domains-containing protein 1 in humans. NLRP1 was the first protein shown to form an inflammasome. NLRP1 is expressed by a variety of cell types, which are predominantly epithelial or hematopoietic. The expression is also seen within glandular epithelial structures including the lining of the small intestine, stomach, airway epithelia and in hairless or glabrous skin. NLRP1 polymorphisms are associated with skin extra-intestinal manifestations in CD. Its highest expression was detected in human skin, in psoriasis and in vitiligo. Polymorphisms of NLRP1 were found in lupus erythematosus and diabetes type 1. Variants of mouse NLRP1 were found to be activated upon N-terminal cleavage by the protease in anthrax lethal factor.

In cell biology, efferocytosis is the process by which apoptotic cells are removed by phagocytic cells. It can be regarded as the 'burying of dead cells'.

<span class="mw-page-title-main">Necroptosis</span> Programmed form of necrosis, or inflammatory cell death

Necroptosis is a programmed form of necrosis, or inflammatory cell death. Conventionally, necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens, in contrast to orderly, programmed cell death via apoptosis. The discovery of necroptosis showed that cells can execute necrosis in a programmed fashion and that apoptosis is not always the preferred form of cell death. Furthermore, the immunogenic nature of necroptosis favors its participation in certain circumstances, such as aiding in defence against pathogens by the immune system. Necroptosis is well defined as a viral defense mechanism, allowing the cell to undergo "cellular suicide" in a caspase-independent fashion in the presence of viral caspase inhibitors to restrict virus replication. In addition to being a response to disease, necroptosis has also been characterized as a component of inflammatory diseases such as Crohn's disease, pancreatitis, and myocardial infarction.

Immunogenic cell death is any type of cell death eliciting an immune response. Both accidental cell death and regulated cell death can result in immune response. Immunogenic cell death contrasts to forms of cell death that do not elicit any response or even mediate immune tolerance.

<span class="mw-page-title-main">Vishva Dixit</span> Kenyan molecular biologist

Vishva Mitra Dixit is a physician of Indian origin who is currently Vice President and Senior Fellow of Physiological Chemistry and Research Biology at Genentech.

<span class="mw-page-title-main">Death regulator Nedd2-like caspase</span> Type of cysteine protease

Death regulator Nedd2-like caspase was firstly identified and characterised in Drosophila in 1999 as a cysteine protease containing an amino-terminal caspase recruitment domain. At first, it was thought of as an effector caspase involved in apoptosis, but subsequent findings have proved that it is, in fact, an initiator caspase with a crucial role in said type of programmed cell death.

References

  1. ↑ "The GlaxoSmithKline Award". www.biochemistry.org. Retrieved 2024-06-10.
  2. ↑ "Trinity researcher Prof Séamus Martin wins 2014 Boyle Medal". The Irish Times. Retrieved 2024-06-10.
  3. ↑ "ANNUAL REVIEW 2005 – 2006" (PDF). Royal Irish Academy. Retrieved 11 June 2024.
  4. ↑ "Find people in the EMBO Communities". people.embo.org.
  5. ↑ "Academy of Europe: Martin Seamus". www.ae-info.org.
  6. ↑ "Curbing the cell stress response". ERC. November 27, 2023.
  7. ↑ "Roitt's Essential Immunology receives BMA Book of the Year Award". News-Medical. October 10, 2012.
  8. ↑ Taylor, Rebecca C.; Cullen, Sean P.; Martin, Seamus J. (March 2008). "Apoptosis: controlled demolition at the cellular level". Nature Reviews Molecular Cell Biology. 9 (3): 231–241. doi:10.1038/nrm2312. ISSN   1471-0080.
  9. ↑ Martin, Seamus J. (July 2016). "Cell death and inflammation: the case for IL ‐1 family cytokines as the canonical DAMP s of the immune system". The FEBS Journal. 283 (14): 2599–2615. doi:10.1111/febs.13775. ISSN   1742-464X.
  10. ↑ Martin, SJ; Reutelingsperger, CP; McGahon, AJ; Rader, JA; van Schie, RC; LaFace, DM; Green, DR (1 November 1995). "Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl". The Journal of experimental medicine. 182 (5): 1545–56. doi:10.1084/jem.182.5.1545. PMID   7595224.
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