Sir Michael John Berridge (22 October 1938 – 13 February 2020) was a British
physiologist
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a subdiscipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out chemical and ...
and
biochemist
Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and Cell (biology), cell parts. The word "biochemist" is a portmanteau of ...
. He was known for his work on
cell signaling
In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...
, in particular the discovery that
inositol trisphosphate acts as a
second messenger
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first m ...
, linking events at the
plasma membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
with the release of
calcium ions (Ca
2+) within the
cell.
Early life and education
Berridge was born in
Gatooma (now
Kadoma, Zimbabwe) in
Southern Rhodesia
Southern Rhodesia was a self-governing British Crown colony in Southern Africa, established in 1923 and consisting of British South Africa Company (BSAC) territories lying south of the Zambezi River. The region was informally known as South ...
(now
Zimbabwe
file:Zimbabwe, relief map.jpg, upright=1.22, Zimbabwe, relief map
Zimbabwe, officially the Republic of Zimbabwe, is a landlocked country in Southeast Africa, between the Zambezi and Limpopo Rivers, bordered by South Africa to the south, Bots ...
). His high school
biology
Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, History of life, origin, evolution, and ...
teacher convinced him and his parents that he should pursue tertiary education, and he entered the newly founded
University of Rhodesia and Nyasaland (now
University of Zimbabwe),
earning his
Bsc in
zoology
Zoology ( , ) is the scientific study of animals. Its studies include the anatomy, structure, embryology, Biological classification, classification, Ethology, habits, and distribution of all animals, both living and extinction, extinct, and ...
and
chemistry
Chemistry is the scientific study of the properties and behavior of matter. It is a physical science within the natural sciences that studies the chemical elements that make up matter and chemical compound, compounds made of atoms, molecules a ...
in 1960.
He became interested in
insect physiology after helping with his
physiology
Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...
professor's research on
tsetse flies, and went to the United Kingdom to study with
Vincent Wigglesworth, regarded as the father of insect physiology, at the Department of Zoology of the
University of Cambridge
The University of Cambridge is a Public university, public collegiate university, collegiate research university in Cambridge, England. Founded in 1209, the University of Cambridge is the List of oldest universities in continuous operation, wo ...
. Berridge became a member at the
Gonville and Caius College, where Wigglesworth was a fellow,
and obtained his PhD in 1965.
Career
Initially intending to return to
Southern Rhodesia
Southern Rhodesia was a self-governing British Crown colony in Southern Africa, established in 1923 and consisting of British South Africa Company (BSAC) territories lying south of the Zambezi River. The region was informally known as South ...
(now
Zimbabwe
file:Zimbabwe, relief map.jpg, upright=1.22, Zimbabwe, relief map
Zimbabwe, officially the Republic of Zimbabwe, is a landlocked country in Southeast Africa, between the Zambezi and Limpopo Rivers, bordered by South Africa to the south, Bots ...
) after his PhD, Berridge's plan was thwarted by the
Rhodesian Bush War
The Rhodesian Bush War, also known as the Rhodesian Civil War, Second as well as the Zimbabwe War of Independence, was a civil conflict from July 1964 to December 1979 in the List of states with limited recognition, unrecognised country U.D.I. ...
. He migrated to the United States instead, joining the Department of
Biology
Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, History of life, origin, evolution, and ...
of the
University of Virginia
The University of Virginia (UVA) is a Public university#United States, public research university in Charlottesville, Virginia, United States. It was founded in 1819 by Thomas Jefferson and contains his The Lawn, Academical Village, a World H ...
as a
postdoctoral fellow.
A year later, he moved to the
Developmental Biology
Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of Regeneration (biology), regeneration, asexual reproduction, metamorphosis, and the growth and di ...
Center of
Case Western Reserve University
Case Western Reserve University (CWRU) is a Private university, private research university in Cleveland, Ohio, United States. It was established in 1967 by a merger between Western Reserve University and the Case Institute of Technology. Case ...
. He became a
research associate under
Bodil Schmidt-Nielsen at the Department of
Biology
Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, History of life, origin, evolution, and ...
of the same university in 1967.
In 1969,
John Treherne invited Berridge to return to the
University of Cambridge
The University of Cambridge is a Public university, public collegiate university, collegiate research university in Cambridge, England. Founded in 1209, the University of Cambridge is the List of oldest universities in continuous operation, wo ...
and join the new Unit of Invertebrate Chemistry and Physiology that he was setting up in the Department of
Zoology
Zoology ( , ) is the scientific study of animals. Its studies include the anatomy, structure, embryology, Biological classification, classification, Ethology, habits, and distribution of all animals, both living and extinction, extinct, and ...
.
He first joined as a senior scientific officer, and was promoted to principal scientific officer in 1972. He became a senior principal scientific officer at the Unit of Insect Neurophysiology and Pharmacology, also at the University of Cambridge, in 1978.
In 1990, Berridge joined the
Babraham Institute
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 buil ...
as the Deputy Chief Scientific Officer of the Laboratory of Molecular Signalling, before serving as the Head of Signalling in 1996 until retiring in 2003. After retirement, Berridge was appointed as Babraham's first emeritus Babraham Fellow.
Berridge was a fellow of the
Trinity College of the University of Cambridge from 1972 until his death.
Berridge maintained an online textbook on
cell signalling
In biology, cell signaling (cell signalling in British English) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in both prokaryotes and eukary ...
, now hosted by
Portland Press under the
Biochemical Society.
Research
Berridge had been studying
cell signaling
In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...
when he was at
Case Western Reserve University
Case Western Reserve University (CWRU) is a Private university, private research university in Cleveland, Ohio, United States. It was established in 1967 by a merger between Western Reserve University and the Case Institute of Technology. Case ...
, where he received advice from Theodore W. Rall, co-discoverer of the
second messenger
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first m ...
cyclic AMP with
Earl Wilbur Sutherland Jr., who had also worked at Case Western Reserve.
Working on the
salivary gland
The salivary glands in many vertebrates including mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of min ...
s of a
blow fly species, Berridge showed cyclic AMP produced the same
physiological
Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...
effect as
serotonin
Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...
, dramatically increasing
saliva
Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which ...
secretion. The idea of second messenger was new at the time, and his finding supported cyclic AMP as a second messenger of serotonin.
He continued studying cyclic AMP after returning to the
University of Cambridge
The University of Cambridge is a Public university, public collegiate university, collegiate research university in Cambridge, England. Founded in 1209, the University of Cambridge is the List of oldest universities in continuous operation, wo ...
, and conducted experiments to study how serotonin and cyclic AMP affected the movement of
ions, as ion concentration difference across the salivary gland
epithelium
Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
controlled the movement of water across the epithelium through
osmosis
Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively permeable membrane, selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of ...
. Berridge measured the
difference in electric potential across the epithelium since ions are
charged.
Surprisingly, he found that serotonin and cyclic AMP produced opposite effect to ion movement. While the former reduced the transepithelial potential difference closer to zero, the latter caused an even more negative difference. This suggested cyclic AMP caused positively-charged ions to move across the epithelium from the
extracellular fluid
In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 50–60% (range 45 to 75%) of total body weight; women and the obese typically ha ...
to the inside of the salivary gland (known as the
lumen).
Berridge suspected
calcium ions (Ca
2+) could explain the distinct electrical but similar physiological effects of serotonin and cyclic AMP. In 1971,
Howard Rasmussen, one of the first researchers to recognise the role of Ca
2+ as a second messenger, was on a
sabbatical
A sabbatical (from the Hebrew: (i.e., Sabbath); in Latin ; Greek: ) is a rest or break from work; "an extended period of time intentionally spent on something that’s not your routine job."
The concept of the sabbatical is based on the Bi ...
at Cambridge.
He and Rasmussen worked together and found serotonin triggered the release of Ca
2+ from a storage inside the
cell. Later, he confirmed that serotonin activated two distinct receptor system, one through cyclic AMP and the other through Ca
2+.
Berridge then wanted to identify the connection between
cell surface receptor
Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integra ...
activation and the release of intracellular Ca
2+ from storage. He was inspired by a review article by Robert H. Michell in 1975, which proposed receptor activation caused the breakdown of
phosphatidylinositol
Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found ...
, which in turn opened
Ca2+ channels on the
cell membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
to allowing Ca
2+ influx into cells. He hypothesised phosphatidylinositol was
hydrolysed into a form of
inositol phosphate and
diglyceride (DAG), and the former was eventually broken down into
inositol. He applied
lithium ions to blow fly salivary glands to inhibit the conversion of inositol phosphate to inositol.
With help from
Rex Malcolm Chaplin Dawson, who was studying inositol at the
Babraham Institute
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 buil ...
near Cambridge, Berridge found that phosphatidylinositol was hydrolysed into
IP3 and DAG. Later the same year, he confirmed IP
3 released Ca
2+ from the intracellular storage, which he identified as the
endoplasmic reticulum
The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
. This report, together with
Yasutomi Nishizuka's discovery that DAG was a
second messenger
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first m ...
in its own right and could activate
protein kinase C
In cell biology, protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...
, marked the start of the field of
calcium signaling.
Awards and honours
*
Fellow
A fellow is a title and form of address for distinguished, learned, or skilled individuals in academia, medicine, research, and industry. The exact meaning of the term differs in each field. In learned society, learned or professional society, p ...
of the
Royal Society
The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
(
1984
Events
January
* January 1 – The Bornean Sultanate of Brunei gains full independence from the United Kingdom, having become a British protectorate in 1888.
* January 7 – Brunei becomes the sixth member of the Association of Southeas ...
)
*
King Faisal International Prize in Science (1986)
*
Louis-Jeantet Prize for Medicine
Established in 1986, the Louis-Jeantet Prizes are funded by the Louis-Jeantet Foundation, ''Fondation Louis-Jeantet'' and awarded each year to experienced researchers who have distinguished themselves in the field of biomedical research in one ...
(1986)
*
William Bate Hardy Prize (1987)
*
Canada Gairdner International Award (1988)
* Member of the
Academia Europaea
The Academia Europaea is a pan-European Academy of humanities, letters, law, and sciences.
The Academia was founded in 1988 as a functioning Europe-wide Academy that encompasses all fields of scholarly inquiry. It acts as co-ordinator of Europe ...
(1989)
*
Baly Medal (1989)
*
Albert Lasker Award for Basic Medical Research (1989)
*
Member
Member may refer to:
* Military jury, referred to as "Members" in military jargon
* Element (mathematics), an object that belongs to a mathematical set
* In object-oriented programming, a member of a class
** Field (computer science), entries in ...
of the
European Molecular Biology Organization (1991)
* Honorary foreign member of the Royal Academy of Medicine of Belgium (Académie royale de médecine de Belgique) (1991)
*
Royal Medal
The Royal Medal, also known as The Queen's Medal and The King's Medal (depending on the gender of the monarch at the time of the award), is a silver-gilt medal, of which three are awarded each year by the Royal Society. Two are given for "the mo ...
(1991)
*
Ciba-Drew Award for Biomedical Research (now
Novartis-Drew Award) (1991)
*
Dr H. P. Heineken Prize for Biochemistry and Biophysics (1994)
*
Wolf Prize in Medicine (1995)
*
Massry Prize (1996)
*
Knight Bachelor
The title of Knight Bachelor is the basic rank granted to a man who has been knighted by the monarch but not inducted as a member of one of the organised Order of chivalry, orders of chivalry; it is a part of the Orders, decorations, and medals ...
(
1998
1998 was designated as the ''International Year of the Ocean''.
Events January
* January 6 – The ''Lunar Prospector'' spacecraft is launched into orbit around the Moon, and later finds evidence for Lunar water, frozen water, in soil i ...
)
* Honorary Fellow of the
Gonville and Caius College, Cambridge (1998)
*
Fellow
A fellow is a title and form of address for distinguished, learned, or skilled individuals in academia, medicine, research, and industry. The exact meaning of the term differs in each field. In learned society, learned or professional society, p ...
of the
Academy of Medical Sciences
The Academy of Medical Sciences is an organisation established in the UK in 1998. It is one of the four UK National Academy, National Academies, the others being the British Academy, the Royal Academy of Engineering and the Royal Society.
Its ...
(1998)
*
Ernst Schering Prize (1999)
*
International Member of the
National Academy of Sciences
The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...
(1999)
* International Honorary Member of the
American Academy of Arts and Sciences
The American Academy of Arts and Sciences (The Academy) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and other ...
(1999)
*
Honorary Fellow of the
Institute of Biology
The Institute of Biology (IoB) was a professional body for biologists, primarily those working in the United Kingdom. The Institute was founded in 1950 by the Biological Council: the then umbrella body for Britain's many learned biological societie ...
(now
Royal Society of Biology) (2000)
* Honorary Member of the
Biochemical Society (2004)
*
Shaw Prize in Life Science and Medicine (2005)
* Member of the
American Philosophical Society
The American Philosophical Society (APS) is an American scholarly organization and learned society founded in 1743 in Philadelphia that promotes knowledge in the humanities and natural sciences through research, professional meetings, publicat ...
(2007)
* Honorary Fellow of the
British Pharmacological Society
The British Pharmacological Society is the primary UK learned society for Pharmacology, pharmacologists, concerned with research into drugs and the ways in which they work. Members work in academia, industry, regulatory agencies, and the health se ...
(2008)
The Sir Michael Berridge Prize at the
Babraham Institute
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 buil ...
was named in his honour and established with his endowment.
References
{{DEFAULTSORT:Berridge, Michael John
1938 births
2020 deaths
Alumni of Gonville and Caius College, Cambridge
British biochemists
British physiologists
Fellows of the Academy of Medical Sciences (United Kingdom)
Fellows of the American Academy of Arts and Sciences
Fellows of the Royal Society
Fellows of Trinity College, Cambridge
Foreign associates of the National Academy of Sciences
Knights Bachelor
Fellows of the Royal Society of Biology
Massry Prize recipients
People from Kadoma, Zimbabwe
Recipients of the Albert Lasker Award for Basic Medical Research
Rhodesian emigrants to the United Kingdom
Rhodesian people of British descent
Royal Medal winners
University of Zimbabwe alumni
White Rhodesian people
Winners of the Heineken Prize
Wolf Prize in Medicine laureates
Members of Academia Europaea
Members of the European Molecular Biology Organization
International members of the American Philosophical Society