Metabolism is a central feature of life – a myriad of biochemical processes that, together, enable organisms to nourish and sustain themselves. Scientists at Cold Spring Harbor Laboratory (CSHL) are in the forefront of efforts to demonstrate how the regulation of genes governs fundamental life processes, including metabolism.
Such research, performed on simple model organisms like yeast cells, has implications for efforts to understand natural processes such as aging and disease states including cancer.
This week a team at CSHL led by Professor Leemor Joshua-Tor, Ph.D., announced a new and unexpected wrinkle in a story they previously thought they understood about how yeast cells, through the action of genes, adjust their metabolism in response to changes in their sources of food. The team’s findings were published February 22 in the journal Science.
Adapting to New Energy Sources
“S. cerevisiae, or common baker’s yeast, can use any number of different types of sugar molecules for energy production,” noted Dr. Joshua-Tor, a structural biologist. “Importantly, the yeast cell can rapidly respond to changes in its nutritional environment by altering the expression of specific genes that allow it to make use of those different energy sources.”
This much, notes Dr. Joshua-Tor and colleagues, has been understood for years. “The players involved in this process have been known for some time. But we did not understand precisely how the components of this particular biochemical pathway worked together,” said Stephen Johnston, a professor at the Biodesign Institute at Arizona State University and a co-author of the study.
It was Dr. Joshua-Tor’s team at CSHL that took the step of investigating the architecture of the proteins involved in the pathway, at the level of individual atoms. Using a technique called x-ray crystallography, they discovered a “player” in the molecular cast of characters whose involvement previously had been overlooked.
The unexpected molecule is called NADP. The team discovered that when a yeast cell changes from using glucose, a simple sugar, as a nutritional source to using galactose, a more complex sugar often found in dairy products and vegetables such as sugar beets, NADP is called into action. It “docks” to a protein called Gal80p, which acts along with a gene regulating-protein called Gal4p, to adapt the metabolism of the yeast cell so that it can make use of galactose.
“Importantly, changes in cellular levels of NAD, a close relative of NADP, had previously been linked to a gene circuit that controls aging and longevity in a large number of different organisms, including yeast but also including animals,” said Professor Rolf Sternglanz of Stony Brook University in New York, a co-author of the study.
Why The Regulatory Cascade Is Important
“It is becoming increasingly clear that the metabolic state of a cell is linked to the expression of its genes in a way that impacts biological processes of many kinds, ranging from cancer to aging,” said Dr. Joshua-Tor. The biochemical cascade identified by the team is part of a complex chain of events whose object is regulation of the output of specific genes.
Not only does the team’s work help explain how links in that gene-regulatory chain are constructed. “Gene-regulatory proteins impact every property of a cell and have long been recognized as possible targets for drugs,” said Dr. Joshua-Tor. “However, these types of proteins have proven resistant to the chemistry of modern drug design. A detailed understanding of how gene regulatory proteins are controlled may offer new and unanticipated opportunities to design drugs that would impact this class of proteins.”
Jim Bono | EurekAlert!
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy