Alireza Mashaghi is a biophysicist and medical scientist at
Leiden University
Leiden University (abbreviated as ''LEI''; nl, Universiteit Leiden) is a Public university, public research university in Leiden, Netherlands. The university was founded as a Protestant university in 1575 by William the Silent, William, Prince o ...
. He is known for his contributions to
single-molecule
A single-molecule experiment is an experiment that investigates the properties of individual molecules. Single-molecule studies may be contrasted with measurements on an ensemble or bulk collection of molecules, where the individual behavior of mo ...
analysis of
chaperone assisted
protein folding
Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...
,
molecular topology
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...
and medical systems biophysics and bioengineering.
Mashaghi made the first observation of direct chaperone involvement during folding of a protein. This work which has been published in Nature solved a long-standing puzzle in biology. In 2017, he reported a new model for chaperone
DnaK
The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an importa ...
function and made a discovery that, according to Ans Hekkenberg, "overturns the decades-old textbook model of action for a protein that is central for many processes in living cells". He and his co-workers found that chaperone DnaK can recognise natively folded protein parts and stabilise them. Inspired by single-molecule analysis of biopolymers, Mashaghi and his team developed a topology framework, termed as
circuit topology
The circuit topology of a folded linear polymer refers to the arrangement of its intra-molecular contacts. Examples of linear polymers with intra-molecular contacts are nucleic acids and proteins. Proteins fold via formation of contacts of variou ...
, which enabled studying folded molecular chains, beyond what
knot theory
In the mathematical field of topology, knot theory is the study of knot (mathematics), mathematical knots. While inspired by knots which appear in daily life, such as those in shoelaces and rope, a mathematical knot differs in that the ends are ...
can offer. Both
knot theory
In the mathematical field of topology, knot theory is the study of knot (mathematics), mathematical knots. While inspired by knots which appear in daily life, such as those in shoelaces and rope, a mathematical knot differs in that the ends are ...
and circuit topology aim to describe chain entanglement. Knot theory considers any entangled chain as a connected sum of
prime knot
In knot theory, a prime knot or prime link is a knot that is, in a certain sense, indecomposable. Specifically, it is a non-trivial knot which cannot be written as the knot sum of two non-trivial knots. Knots that are not prime are said to be co ...
s, which are themselves undecomposable. Circuit topology splits any entangled chains (including prime knots) into basic structural units called soft contacts, and lists simple rules how soft contacts can be put together. An advantage of circuit topology is that it can be applied to open linear chains with intra-chain interactions, so called hard contacts. This enabled topological analysis of proteins and genomes, which are often described as "unknot" in knot theory.
Mashaghi also contributed to others areas in biophysics and bioengineering including
membrane
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
biophysics and membrane sensing, nanoparticle technology, and
organ-on-a-chip
An organ-on-a-chip (OOC) is a multi-channel 3-D microfluidic cell culture, integrated circuit (chip) that simulates the activities, mechanics and physiological response of an entire organ or an organ system, a type of artificial organ. It cons ...
technology. In particular, the Mashaghi team was one of the first to introduce Organ Chip technology to the field of
virology
Virology is the Scientific method, scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host (biology), ...
. For example, his team engineered the first chip-based disease model for
Ebola
Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after becom ...
hemorrhagic shock syndrome. Ebola and similar viruses pathologically alter the mechanics of human cells, which is recapitulated in organ chip models. Moreover, the Mashaghi team developed
optical tweezers
Optical tweezers (originally called single-beam gradient force trap) are scientific instruments that use a highly focused laser beam to hold and move microscopic and sub-microscopic objects like atoms, nanoparticles and droplets, in a manner simila ...
and acoustic
force spectroscopy Force spectroscopy is a set of techniques for the study of the interactions and the binding forces between individual molecules. These methods can be used to measure the mechanical properties of single polymer molecules or proteins, or individual c ...
based assays to probe such mechanical alterations at the single cell level.
Mashaghi is also active in interdisciplinary research in
ophthalmology
Ophthalmology ( ) is a surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders.
An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a medic ...
and clinical medicine. In 2017, he and his co-workers at Harvard developed an immunotherapy strategy to improve survival of
cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...
grafts. The work which gained significant media attention, provides hope for patients with inflamed cornea bed, typically suffering from high graft rejection rates. Together with his co-workers, he contributed to the use of
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
technology,
omics
The branches of science known informally as omics are various disciplines in biology whose names end in the suffix '' -omics'', such as genomics, proteomics, metabolomics, metagenomics, phenomics and transcriptomics. Omics aims at the collect ...
technology, and systems biophysics approaches in ophthalmology. Furthermore, in their research, Alireza Mashaghi and his team are linking
statistical physics
Statistical physics is a branch of physics that evolved from a foundation of statistical mechanics, which uses methods of probability theory and statistics, and particularly the Mathematics, mathematical tools for dealing with large populations ...
and
medical diagnostics
Medical diagnosis (abbreviated Dx, Dx, or Ds) is the process of determining which disease or condition explains a person's symptoms and signs. It is most often referred to as diagnosis with the medical context being implicit. The information re ...
; this unprecedented link between physics and medicine may allow for early and efficient diagnosis of certain diseases.
During his academic career, Mashaghi has been affiliated with various institutions including
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
,
Leiden University
Leiden University (abbreviated as ''LEI''; nl, Universiteit Leiden) is a Public university, public research university in Leiden, Netherlands. The university was founded as a Protestant university in 1575 by William the Silent, William, Prince o ...
,
Massachusetts Institute of Technology
The Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. Established in 1861, MIT has played a key role in the development of modern technology and science, and is one of the ...
,
Delft University of Technology
Delft University of Technology ( nl, Technische Universiteit Delft), also known as TU Delft, is the oldest and largest Dutch public technical university, located in Delft, Netherlands. As of 2022 it is ranked by QS World University Rankings among ...
,
ETH Zurich
(colloquially)
, former_name = eidgenössische polytechnische Schule
, image = ETHZ.JPG
, image_size =
, established =
, type = Public
, budget = CHF 1.896 billion (2021)
, rector = Günther Dissertori
, president = Joël Mesot
, ac ...
,
Max Planck Institutes
The Max Planck Society for the Advancement of Science (german: Max-Planck-Gesellschaft zur Förderung der Wissenschaften e. V.; abbreviated MPG) is a formally independent non-governmental and non-profit association of German research institutes. ...
, and
AMOLF. Mashaghi has published more that 100 papers in peer-reviewed scientific journals including several papers in
Nature
Nature, in the broadest sense, is the physics, physical world or universe. "Nature" can refer to the phenomenon, phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. ...
and Nature specialty journals. He worked and co-authored with
Cees Dekker
Cornelis "Cees" Dekker (born 7 April 1959 in Haren, Groningen) is a Dutch physicist, and Distinguished University Professor at the Technical University of Delft. He is known for his research on carbon nanotubes, single-molecule biophysics, and na ...
,
Anthony A. Hyman
Anthony Arie Hyman (born 27 May 1962) is a British scientist and director at the Max Planck Institute of Molecular Cell Biology and Genetics.
Education
Hyman was educated William Ellis School, University College London and the University of ...
,
Colin Adams,
Donald E. Ingber
Donald E. Ingber (born 1956) is an American cell biology, cell biologist and bioengineering, bioengineer. He is the founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University,Crow, James Mitchell (19 Janua ...
,
Huib Bakker
Huib Johan Bakker (born 2 March 1965) is a Dutch physicist working in the field of ultrafast spectroscopy. He has been president of research institute AMOLF since 1 February 2016.
Career
Bakker was born on 2 March 1965 in Haarlem. He studied phys ...
,
Reza Dana, and
Petra Schwille
Petra Schwille (born 25 January 1968 in Sindelfingen) is a German professor and a researcher in the area of biophysics.
Since 2011, she has been a director of the Department of Cellular and Molecular Biophysics at the Max Planck Institute for Bi ...
. He serves on editorial board of several journals including
Nano Research and
Scientific Reports
''Scientific Reports'' is a peer-reviewed open-access scientific mega journal published by Nature Portfolio, covering all areas of the natural sciences. The journal was established in 2011. The journal states that their aim is to assess solely th ...
.
In 2018, Mashaghi has been named as "Discoverer of the Year" by Leiden University.
Our Talents & Discoveries 2017 - Universiteit Leiden
/ref> He is the recipient of several awards including an honorarium from American Chemical Society
The American Chemical Society (ACS) is a scientific society based in the United States that supports scientific inquiry in the field of chemistry. Founded in 1876 at New York University, the ACS currently has more than 155,000 members at all d ...
.
References
{{DEFAULTSORT:Mashaghi, Alireza
Year of birth missing (living people)
Living people
Physician-scientists
Biophysicists
Dutch ophthalmologists
Harvard University staff
Leiden University faculty
ETH Zurich alumni