Nav: Home

A new model of metabolism draws from thermodynamics and 'omics'

January 13, 2020

All living things are made of carbon, and sugars, e.g. glucose, are a very common source of it. Consequently, most cells are good at eating sugars, using enzymes to digest them through a series of chemical reactions that transform the initial sugar into a variety of cell components, including amino acids, DNA building blocks, and fats. Because they help these sugar-metabolism reactions run efficiently, the enzymes called biocatalysts.

Given how critical all enzymes are to life itself, scientists have built several mathematical models that describe how the cells use enzymes to transform a sugar. Such models have been successfully used, for instance, to improve 2nd generation biofuel production or identify drug targets for malaria, but they don't take into account the metabolic "cost" of producing the enzymes that catalyze all these chemical reactions.

Accounting for this phenomenon, called "expression", is key to describing many other phenomena, including beer fermentation and the growth of cancer cells. But all this first depends on accurately modeling the mechanisms of expression.

Now, Professor Vassily Hatzimanikatis at EPFL and Pierre Salvy, a PhD student in his lab, have developed a mathematical model that can efficiently model the expression of enzymes in living cells, as well as its associated metabolic cost. The model is called ETFL for "Expression and Thermodynamics Flux" and draws its accuracy from taking into account both biochemistry and thermodynamics - a set of physico-chemical laws that describe how energy flows in systems. Combining this with mathematical tools from the field of optimization, the researchers were able to drastically improve the accuracy of the model's predictions.

"This integration of metabolism, expression, and thermodynamics is the first of its kind, and is 10 to 100 times faster than the previous state-of-the-art models, which do not feature thermodynamics," says Salvy.

To further increase its predictive power, the ETFL model was designed to take into account a wide variety of measurements made through the massive field of "omics", which measures characteristics of cells such as gene expression, protein profiles etc. "Our algorithm can be used to improve the production of biochemical products, or to accurately predict how cancer cells metabolize," says Salvy. "It can also open the door to applications in personalized medicine."
-end-
Reference

Pierre Salvy, Vassily Hatzimanikatis. The ETFL formulation allows multi-omics integration in thermodynamics-compliant metabolism and expression models. Nature Communications 13 January 2020. DOI: 10.1038/s41467-019-13818-7

Ecole Polytechnique Fédérale de Lausanne

Related Cancer Cells Articles:

New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed
Scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill some multiplying human breast cancer cells by selectively attacking the core of their cell division machinery.
Breast cancer cells use message-carrying vesicles to send oncogenic stimuli to normal cells
According to a Wistar study, breast cancer cells starved for oxygen send out messages that induce oncogenic changes in surrounding normal epithelial cells.
Breast cancer cells turn killer immune cells into allies
Researchers at Johns Hopkins University School of Medicine have discovered that breast cancer cells can alter the function of immune cells known as Natural killer (NK) cells so that instead of killing the cancer cells, they facilitate their spread to other parts of the body.
Breast cancer cells can reprogram immune cells to assist in metastasis
Johns Hopkins Kimmel Cancer Center investigators report they have uncovered a new mechanism by which invasive breast cancer cells evade the immune system to metastasize, or spread, to other areas of the body.
Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.
New liver cancer research targets non-cancer cells to blunt tumor growth
'Senotherapy,' a treatment that uses small molecule drugs to target ''senescent'' cells, or those cells that no longer undergo cell division, blunts liver tumor progression in animal models according to new research from a team led by Celeste Simon, PhD, a professor of Cell and Developmental Biology in the Perelman School of Medicine at the University of Pennsylvania and scientific director of the Abramson Family Cancer Research Institute.
Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.
Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.
First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.
Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.
More Cancer Cells News and Cancer Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Debbie Millman: Designing Our Lives
From prehistoric cave art to today's social media feeds, to design is to be human. This hour, designer Debbie Millman guides us through a world made and remade–and helps us design our own paths.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Insomnia Line
Coronasomnia is a not-so-surprising side-effect of the global pandemic. More and more of us are having trouble falling asleep. We wanted to find a way to get inside that nighttime world, to see why people are awake and what they are thinking about. So what'd Radiolab decide to do?  Open up the phone lines and talk to you. We created an insomnia hotline and on this week's experimental episode, we stayed up all night, taking hundreds of calls, spilling secrets, and at long last, watching the sunrise peek through.   This episode was produced by Lulu Miller with Rachael Cusick, Tracie Hunte, Tobin Low, Sarah Qari, Molly Webster, Pat Walters, Shima Oliaee, and Jonny Moens. Want more Radiolab in your life? Sign up for our newsletter! We share our latest favorites: articles, tv shows, funny Youtube videos, chocolate chip cookie recipes, and more. Support Radiolab by becoming a member today at Radiolab.org/donate.