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Dr. Denis Alexander has spent 40 years in the biomedical research community. He is an Emeritus Fellow of St. Edmund’s College, Cambridge and an Emeritus Director of the Faraday Institute for Science and Religion, Cambridge which he co-founded with Bob White in 2006.
Alexander was an Open Scholar at St Peter's College, Oxford, where he studied Biochemistry under the late Arthur Peacocke. He studied for a PhD in Neurochemistry at the Institute of Psychiatry, where he analysed the molecular structure of the sodium-potassium pump.
He spent 15 years in various university departments and laboratories outside the United Kingdom (1971–1986), including a post at Hacettepe University (1972–1974) and the Middle East Technical University (1974–1980) in Ankara, Turkey, where he set up a neurochemistry laboratory in the newly formed Biological Sciences Department. From 1981–1986 he held the post of Associate Professor of Biochemistry at the American University of Beirut Medical Centre, Lebanon, where he helped to establish the National Unit of Human Genetics. This entailed establishing a new research laboratory in medical genetics and the first prenatal diagnostic clinic in the Arab World. Discoveries during this era included a novel mutation which affected lysosomal enzyme processing and the identification and characterisation of several rare genetic diseases. At a symposium at the American University of Beirut Medical Center on ‘Genetic Diseases in Lebanon’ held in April 1985, Alexander reported that “over 50 highly specialised tests are performed in the unit’s laboratories, making them the leading laboratories in the whole Arab World”. Alexander and his family were evacuated three times from West Beirut, the first time following the Israeli invasion of the Lebanon in June 1982, the second time following intensive fighting that broke out amongst armed factions in March 1984, and the third and final time following Reagan’s bombing of Libya in April 1986 which led to retaliation against the few westerners still residing in West Beirut. The Alexander family left West Beirut the same week that John McCarthy and Brian Keenan were kidnapped.
Upon return to the UK Alexander switched research fields and obtained a post at the Imperial Cancer Research Laboratories in London (now Cancer Research UK) (1986–1989) where he developed a new research programme on protein phosphatases in T cells. Following this Alexander became Project Leader at The Babraham Institute, Cambridge (1989-2008) where he subsequently headed the Molecular Immunology Programme and established the Laboratory of Lymphocyte Signalling and Development. Research focused on the role of Protein tyrosine phosphatases in lymphocyte signalling, development, activation and oncology. This led to a series of publications on CD45 (also known as PTPRC), on SHP-2 (also known as PTPN11), on the use of therapeutic monoclonal antibodies, and on the discovery of a novel signaling pathway utilizing intracellular alkalinisation following DNA damage implicated in the development of cancer.
During his time at The Babraham Institute, Alexander served on the Babraham Executive Committee from 1997-2006 and was elected a Fellow of St Edmund's College, Cambridge, in 1997.
Alexander has written on the subject of science and religion since at least 1972, when his book 'Beyond Science', written at the age of 25/26, was reviewed by Hugh Montefiore, then Bishop of Kingston upon Thames in the New Scientist.
In the late 1980s he became a member of the National Committee of Christians in Science [www.cis.org.uk] and served on the Committee until 2013. In 1992 he became editor of the journal Science and Christian Belief, a post he held until 2013. Alexander served on the Executive Committee of the International Society for Science and Religion and is a member of the Cambridge Papers Writing Group for which he writes papers related to science and religion.
In January 2006 Alexander became the founding Director of the Faraday Institute for Science and Religion which was originally founded as part of St Edmund's College, Cambridge, and launched with a grant from the John Templeton Foundation. Alexander co-founded the Institute with Bob White. The Institute carries out research on science and religion, runs courses, and engages in academic dissemination on the topic through seminars, lectures, panel discussions and in schools. In October 2012 Alexander became Emeritus Director and is now Chair of the Board of Trustees of the Institute. In December 2012 Alexander gave the Gifford Lectures at St Andrews University on the theme "Genes, Determinism and God". Alexander writes and lectures widely on science and religion. His book Rebuilding the Matrix – Science and Faith in the 21st Century was published in 2002. Alexander is well-known for his critique of creationism and of "intelligent design". [1]
Alexander engages in the public understanding of science and religion. This includes articles published on web-sites such as Nature, The Guardian and The Huffington Post. TV programmes such as David Malone's Testing God documentary for Channel 4, Rod Liddle’s Channel 4 programme The Trouble with Atheism and a series of interviews for the US "Closer to Truth" TV series, together with numerous radio discussions and interviews, such as his interview with Joan Bakewell in her BBC series "Belief", [2] on Australian national radio, and radio debates with Stephen Law and P.Z. Myers. In 2018 Alexander spoke in favour of the motion "This House Believes that Science Alone Can Never Answer our Biggest Questions" at an Oxford Union debate.
A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase. The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets. Most of the others are tyrosine kinases, although additional types exist. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction.
The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through the process of transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors. Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.
Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration.
The Babraham Institute is a life sciences research institution focussing on healthy ageing. The Babraham Institute is based on the Babraham Research Campus, partly occupying a former manor house, but also laboratory and science facility buildings on the campus, surrounded by an extensive parkland estate, just south of Cambridge, England. It is an independent and charitable organization which is involved in biomedical research, including healthy aging and molecular biology. The director is Dr Simon Cook who also leads the Institute's signalling research programme.
Protein tyrosine phosphatases (EC 3.1.3.48, systematic name protein-tyrosine-phosphate phosphohydrolase) are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins:
Lck is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. The Lck is a member of Src kinase family (SFK) and is important for the activation of T-cell receptor (TCR) signaling in both naive T cells and effector T cells. The role of Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the constitutive activity of the mouse Lck homolog varies among memory T cell subsets. It seems that in mice, in the effector memory T cell (TEM) population, more than 50% of Lck is present in a constitutively active conformation, whereas less than 20% of Lck is present as active form in central memory T cells. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.
Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. The receptors are generally activated by dimerization and substrate presentation. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.
The Faraday Institute for Science and Religion is an interdisciplinary academic research institute based in Cambridge, England. It is named after the 19th-century English scientist Michael Faraday, the pioneer of electromagnetic induction.
Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase (PTP) Shp2.
Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the PTPRC gene. PTPRC is also known as CD45 antigen, which was originally called leukocyte common antigen (LCA).
Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the MAPK3 gene.
Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the PTPN6 gene.
M-phase inducer phosphatase 1 also known as dual specificity phosphatase Cdc25A is a protein that in humans is encoded by the cell division cycle 25 homolog A (CDC25A) gene.
Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B (PTP1B) is an enzyme that is the founding member of the protein tyrosine phosphatase (PTP) family. In humans it is encoded by the PTPN1 gene. PTP1B is a negative regulator of the insulin signaling pathway and is considered a promising potential therapeutic target, in particular for treatment of type 2 diabetes. It has also been implicated in the development of breast cancer and has been explored as a potential therapeutic target in that avenue as well.
Dual specificity protein phosphatase 1 is an enzyme that in humans is encoded by the DUSP1 gene.
Receptor-type tyrosine-protein phosphatase alpha is an enzyme that in humans is encoded by the PTPRA gene.
Protein tyrosine phosphatase non-receptor type 7 is an enzyme that in humans is encoded by the PTPN7 gene.
A non-receptor tyrosine kinase (nRTK) is a cytosolic enzyme that is responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell.
Kinetic-segregation is a model proposed for the mechanism of T-cell receptor (TCR) triggering. It offers an explanation for how TCR binding to its ligand triggers T-cell activation, based on size-sensitivity for the molecules involved. Simon J. Davis and Anton van der Merwe, University of Oxford, proposed this model in 1996. According to the model, TCR signalling is initiated by segregation of phosphatases with large extracellular domains from the TCR complex when binding to its ligand, allowing small kinases to phosphorylate intracellular domains of the TCR without inhibition. Its might also be applicable to other receptors of the Non-catalytic tyrosine-phosphorylated receptors family such as CD28.
Non-catalytic tyrosine-phosphorylated receptors (NTRs), also called immunoreceptors or Src-family kinase-dependent receptors, are a group of cell surface receptors expressed by leukocytes that are important for cell migration and the recognition of abnormal cells or structures and the initiation of an immune response. These transmembrane receptors are not grouped into the NTR family based on sequence homology, but because they share a conserved signalling pathway utilizing the same signalling motifs. A signaling cascade is initiated when the receptors bind their respective ligand resulting in cell activation. For that tyrosine residues in the cytoplasmic tail of the receptors have to be phosphorylated, hence the receptors are referred to as tyrosine-phosphorylated receptors. They are called non-catalytic receptors, as the receptors have no intrinsic tyrosine kinase activity and cannot phosphorylate their own tyrosine residues. Phosphorylation is mediated by additionally recruited kinases. A prominent member of this receptor family is the T-cell receptor.
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