Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene screen reveals 2-way communication between common biological pathways and body's daily clock

21.09.2009
Insulin, folate metabolism influence circadian rhythms, according to Penn study

While scientists have known for several years that our body's internal clock helps regulate many biological processes, researchers have found that the reverse is also true: Many common biological processes – including insulin metabolism – regulate the clock, according to a new study by investigators at the University of Pennsylvania School of Medicine, the Genomics Institute of the Novartis Research Foundation, and the University of California at San Diego.

The new data, published online in Cell this week, suggest that someday physicians may be able to use small molecules that inhibit or stimulate these biological processes in order to influence a person's clock when it gets out of sync due to jetlag or shift work, and to devise new ways to treat metabolic disorders that are intimately tied to the body's daily cycles.

Using a genome-wide screen, the investigators found that reducing expression of any one of hundreds of genes could substantially alter the length of the circadian cycle, which controls the 24-hour sleep/wake cycle. The clock-influencing genes are involved in a large number of biological processes, but the researchers found that components of insulin metabolism, folate metabolism, and the cell cycle were overrepresented in the gene screen, suggesting that these pathways are closely linked to the clock.

"Clock biologists all appreciated that the communication went one direction – from the clock to biological processes – but I don't think anyone anticipated that there would be this level of integration with cell metabolism and the cell cycle, or all these other pathways impinging on clock function," says John Hogenesch, PhD, Associate Professor of Pharmacology in the Institute for Translational Medicine and Therapeutics at Penn. Hogenesch is a co-senior author on the paper with Steve Kay, Dean of the Division of Biological Sciences at UCSD. "There were some hints this might occur for some genes, but not to this extent."

The idea that biological processes might have feedback systems with the circadian clock makes some sense to Hogenesch. For example, he points to the influence of insulin metabolism, saying "If your energy requirements aren't being met, instead of spending a lot of energy on a cell division, a cell might necessarily delay it. It is the same strategy we use when we are not ready to do something, we delay. Maybe procrastination is an evolutionary cellular strategy enabled by the clock to confront situations where resources are limited."

While biologists regularly draw molecular pathways as if they are distinct from one another, they know the reality is much different. "This is a good example showing how dozens of pathways are functionally interconnected with clock function and vice versa," Hogenesch says. "It is important to remember that when you start to change function with a drug, for example, that the perturbation can have unanticipated consequence. Sometimes these consequences are good, but sometimes not."

Hogenesch stresses that while the new experiments show a feedback loop between biological processes and the clock in individual cells in culture, it is not yet clear how feedback systems work in the whole organism. Currently the team is working on biochemical and genetic experiments to answer that question.

In addition to publishing the data in the journal, the investigators have displayed the data on the BioGPS open-access searchable database (http://biogps.gnf.org). The circadian genome-wide screen data can be found at http://biogps.gnf.org/circadian/ and are linked to expression data from Penn, gene function data at Wikipedia and the National Center for Biotechnology Information (NCBI), as well as gene structure information from the University of California at Santa Cruz.

Hogenesch, who helped develop the website when he worked at the Genomics Institute of the Novartis Research Foundation in San Diego, said the site relies on web 2.0 technology and is very simple to use and customize. He and his colleagues built the site because many researchers want to do large database searches but are not computer scientists or informatics specialists. "Andy Su [of Novartis] and I decided to develop a site that even my mom could use, and pitched at the 90% of biologists who want to use something but don't have the skill sets. We decided to build something that would allow them to take advantage of large datasets such as this one."

Co-first authors on the paper are Eric E. Zhang and Tsuyoshi Hirota of the Genomics Institute of the Novartis Research Foundation, and UCSD, and Andrew C. Liu, of the Genomics Institute of the Novartis Research Foundation and the University of Memphis, Tenn. Other authors on the paper include Loren J. Miraglia, Genevieve Welch, Xianzhong Liu, Jon W. Huss III, Jeff Janes, and Andrew I. Su of the Genomics Institute of the Novartis Research Foundation, and Pagkapol Y. Pongsawakul, Ann Atwood, and Steve A. Kay of UCSD.

This research was funded by Silvio O. Conte Center and the National Institute of Mental Health.

PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to the National Institutes of Health, received over $366 million in NIH grants (excluding contracts) in the 2008 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's top ten "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center, named one of the nation's "100 Top Hospitals" for cardiovascular care by Thomson Reuters. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine at Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.

Karen Kreeger | EurekAlert!
Further information:
http://www.upenn.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

Researchers make flexible glass for tiny medical devices

24.03.2017 | Materials Sciences

Laser activated gold pyramids could deliver drugs, DNA into cells without harm

24.03.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>