Contact Information:

Media Contact

Robbie Loewith

Twitter: UNIGEnews

Kredyty mieszkaniowe Kredyty mieszkaniowe

Sprawdź aktualny ranking najlepszych kredytów mieszkaniowych w Polsce - atrakcyjne kredytowanie nieruchomości. - Press Release Distribution
RSS - Press News Release
Add Press Release

A new tool to study an important anti-cancer and immunosuppressive target

Structure explains why protein becomes insensitive to its inhibitor rapamycin

( The chemical rapamycin is used clinically as an immunosuppressant and as an anti-cancer agent that works by inactivating a protein named TOR (Target Of Rapamycin). This protein is essential for the growth of normal cells, but is hyperactive in tumor cells. To be able to carry out its various growth-related tasks, TOR needs to assemble into one of two larger protein complexes named TORC1 and TORC2. Curiously, whereas TORC1 is inhibited by rapamycin, TORC2 is unaffected by this drug. The team of Robbie Loewith, professor in biology at the University of Geneva (UNIGE), Switzerland, has just lifted the veil on this mystery. Their study, published in the journal Molecular Cell, describes the structure of TORC2 and explains why rapamycin cannot access the TOR protein in this complex. These results enabled the team to generate a variant of TORC2 in which TOR is unprotected. This variant, which is sensitive to rapamycin, provides researchers in the field with a new tool to study TORC2 function in cells. The elucidation of the structure and function of this complex serves as a crucial step in the ongoing effort to identify clinically important drugs with which this important signaling pathway can be targeted.

When researchers brought back simple soil samples from an expedition to Easter Island in the 1960s, little did they know that they had stumbled upon a real treasure. Back in the lab, it was discovered that this soil contained the bacterium Streptomyces hygroscopicus. It produced a natural compound known as rapamycin (derived from Easter Island's native name Rapa Nui), that was subsequently found to be a powerful antifungal agent. However, this use was abandoned with the discovery of the immunosuppressive and anti-cancer properties of rapamycin. Nowadays, it is used in transplant patients to prevent the rejection of the new organ. It also shows great promise for the development of new cancer drugs.

How does rapamycin work? The first step was to identify its target: an intracellular protein named TOR (Target Of Rapamycin), which stimulates the growth of cells. As a Post-Doctoral Fellow, Robbie Loewith discovered that TOR needs to assemble into one of two larger protein complexes named TORC1 and TORC2 to carry out its various tasks. Surprisingly, TORC1 but not TORC2 was found to be inhibited by rapamycin. Why the latter is insensitive to this chemical had remained a mystery for more than a decade.

Challenging to study The ability to inhibit TORC1 with rapamycin made it relatively straightforward to study its functions. In contrast, lacking a rapamycin-equivalent has made it much more difficult to study TORC2 signaling. "In order to more easily study TORC2, we wanted to learn how to make this complex sensitive to rapamycin" says Robbie Loewith, researcher at the Department of Molecular Biology of the Faculty of Science from the UNIGE, Switzerland.

Thanks to an international collaboration, led by the scientist within the National Centre of Competence in Research (NCCR) 'Chemical Biology', the answer to this and several other essential questions are now clear. "First, we determined the structure of TORC2 and were able to visualize how proteins of this complex are organized in three dimensions", details Christl Gaubitz, a PhD student within the Geneva group and co-lead author of the article. "From this we observed which subunit within TORC2 was obstructing the rapamycin-binding site on TOR".

The researchers thus discovered why rapamycin does not act on TORC2: "By deleting part of this subunit we generated a variant of TORC2 sensitive to rapamycin", explains co-lead author Manoel Prouteau. Equipped with this new tool, the biologists were able to study how TORC2 acts to stimulate cell growth.

Inhibit tumors on both fronts Due to their fast proliferation, tumor cells have an increased dependency on TORC1 and thus are hyper-sensitive to rapamycin. However, this is not without side-effects. "From our present work we hope to one day identify a specific inhibitor of endogenous TORC2 which could also find use as an effective anti-cancer agent ", concludes Taiana Oliveira, a researcher in the group of Christiane Schaffitzel at the European Laboratory of Molecular Biology, in Grenoble, France, and third co-lead author of the study.



Bladder cells regurgitate bacteria to prevent UTIs

DURHAM, N.C. -- Duke Medicine researchers have found that bladder cells have a highly effective way to combat E. coli bacteria that cause urinary tract infections (UTIs). In a study published online May 28, 2015, in the journal Cell, Duke researchers and their colleagues describe how bladder cells can physically eject the UTI-causing bacteria that manage to invade the host cell. This response is analogous to having indigestion and vomiting to rid the stomach of harmful substances. The finding suggests there may be a potential way to capitalize on this natural tendency ...

Out of Africa via Egypt

New research suggests that European and Asian (Eurasian) peoples originated when early Africans moved north - through the region that is now Egypt - to expand into the rest of the world. The findings, published in the American Journal of Human Genetics, answer a long-standing question as to whether early humans emerged from Africa by a route via Egypt, or via Ethiopia. The extensive public catalogue of the genetic diversity in Ethiopian and Egyptian populations developed for the project also now provides a valuable, freely available, reference panel for future medical ...

How we make emotional decisions

CAMBRIDGE, MA -- Some decisions arouse far more anxiety than others. Among the most anxiety-provoking are those that involve options with both positive and negative elements, such choosing to take a higher-paying job in a city far from family and friends, versus choosing to stay put with less pay. MIT researchers have now identified a neural circuit that appears to underlie decision-making in this type of situation, which is known as approach-avoidance conflict. The findings could help researchers to discover new ways to treat psychiatric disorders that feature impaired ...

Sanford-Burnham researchers identify a new target for treating drug-resistant melanoma

La Jolla, Calif., May 28, 2015 - A new collaborative study led by researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham), published today in Cell Reports, provides new insight into the molecular changes that lead to resistance to a commonly prescribed group of drugs called BRAF inhibitors. The findings suggest that targeting newly discovered pathways could be an effective approach to improving the clinical outcome of patients with BRAF inhibitor-resistant melanoma tumors. Melanoma is the deadliest form of skin cancer, killing more than 8,000 people ...

Sleep quality influences the cognitive performance of autistic and neurotypical children

Sleep quality influences the cognitive performance of autistic and neurotypical children
This news release is available in French. One night of poor sleep significantly decreases performance on intelligence tests in children with autism spectrum disorder (ASD) and also in neurotypical children (without ASD). This is the conclusion made by researchers at the Hôpital Rivière-des-Prairies, affiliated with the Institut universitaire en santé mentale de Montréal and Université de Montréal. For a paper published in the International Journal of Psychophysiology, the researchers observed the EEG measures of 13 autistic children ...

Health factors influence ex-prisoners' chances of returning to jail

Ex-prisoners with a history of risky drug use, mental illness or poverty are more likely to end up back behind bars. Those who are obese, are chronically ill or have attempted suicide are more likely to remain in the community. These are some of the findings from an exploratory study into health-related factors that could be used to predict whether a person released from prison will end up in custody again. It was led by Emma Thomas of the University of Melbourne in Australia and is published in Springer's journal Health & Justice, an open access journal. In many countries, ...

Public raises alarm about ineffectiveness of some Montagu's harrier conservation measures

Public raises alarm about ineffectiveness of some Montagus harrier conservation measures
A citizen science programme reveals the protection measures for the Montagu's harrier in the cereal crop season in France to be ineffective if nests are not protected to decrease predation after harvesting. A study has been published as a result of this voluntary fieldwork, with the participation of the Hunting Resources Research Institute, which proposes fencing off the nests as a way of mitigating the damage and optimising conservation efforts in different areas. Over the last decade there has been an explosion in the so-called citizen science programmes, in which people ...

In battle of the sexes, a single night with a New York male is enough to kill

In battle of the sexes, a single night with a New York male is enough to kill
EUGENE, Ore. -- (May 28, 2015) -- Men and women often enter relationships with different long-term goals. In the animal world, differences in approaches to reproductive success can lead to sexual conflict. Male fruit flies, for example, transfer proteins during mating that can alter the timing of a female's egg laying and her tendency to later mate with other males. Some of these male-derived proteins also migrate from the female's reproductive tract to her brain. Now, in a new study, scientists of the University of Oregon and Bowdoin College show that sexual conflicts ...

Research roundup from Penn's Abramson Cancer Center

CHICAGO -- Researchers from the Abramson Cancer Center of the University of Pennsylvania and Penn's Perelman School of Medicine will present results from several clinical trials and other key studies during the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting from May 29 through June 2. Results of Phase II Trial Show Successful Antitumor Response Rate in Patients with Advanced BRCA-Related Ovarian Cancer Olaparib, an experimental twice-daily oral cancer drug, produces significant antitumor responses in more than a third of patients with BRCA-related ...

Peek eye testing app shown to work as well as charts for visual acuity

An app to test eyesight easily and affordably using a smartphone is as accurate as traditional charts, according to a study published today. Peek (the Portable Eye Examination Kit) is a unique smartphone-based system for comprehensive eye testing anywhere in the world which has been designed and developed by the London School of Hygiene & Tropical Medicine, the University of Strathclyde and the NHS Glasgow Centre for Ophthalmic Research. Globally, 285 million people are visually impaired and 80% have diseases which could be cured or prevented. However, most live in ...


How your brain decides blame and punishment -- and how it can be changed

Uniquely human brain region enables punishment decisions

Pinpointing punishment

Chapman University publishes research on attractiveness and mating

E-cigarettes: Special issue from Nicotine & Tobacco Research

Placental problems in early pregnancy associated with 5-fold increased risk of OB & fetal disorders

UT study: Invasive brood parasites a threat to native bird species

Criminals acquire guns through social connections

Restoring ocean health

Report: Cancer remains leading cause of death in US Hispanics

Twin study suggests genetic factors contribute to insomnia in adults

To be fragrant or not: Why do some male hairstreak butterflies lack scent organs?

International team discovers natural defense against HIV

Bolivian biodiversity observatory takes its first steps

Choice of college major influences lifetime earnings more than simply getting a degree

Dominant strain of drug-resistant MRSA decreases in hospitals, but persists in community

Synthetic biology needs robust safety mechanisms before real world application

US defense agencies increase investment in federal synthetic biology research

Robots help to map England's only deep-water Marine Conservation Zone

Mayo researchers identify protein -- may predict who will respond to PD-1 immunotherapy for melanoma

How much water do US fracking operations really use?

New approach to mammograms could improve reliability

The influence of citizen science grows despite some resistance

Unlocking secrets of how fossils form

What happens on the molecular level when smog gets into the lungs?

Using ultrasound to clean medical instruments

Platinum and iron oxide working together get the job done

Tiny silica particles could be used to repair damaged teeth, research shows

A quantum lab for everyone

No way? Charity's logo may influence perception of food in package

[] A new tool to study an important anti-cancer and immunosuppressive target
Structure explains why protein becomes insensitive to its inhibitor rapamycin is a service of DragonFly Company. All Rights Reserved.
Issuers of news releases are solely responsible for the accuracy of their content.