Study Reveals Importance Of Timing For Cellular Signals, Suggests Possible Tactic For Cancer Therapeutics
Magic tricks work because they take advantage of the brain’s sensory assumptions, tricking audiences into seeing phantoms or overlooking sleights of hand. Now a team of UC San Francisco researchers has discovered that even brainless single-celled yeast have sensory biases that can be hacked by a carefully engineered illusion, a finding that could be used to develop new approaches to fighting diseases such as cancer.
“The ability to perceive and respond to the environment is a basic attribute of all living organisms, from the greatest to the smallest,” said Wendell Lim, PhD, the study’s senior author. “And so is the susceptibility to misperception. It doesn’t matter if the illusion is based on molecular sensors within a single cell or neurons in the brain.”
In the new study, published online Nov. 19, 2015 in Science Express, Lim and his team discovered that yeast cells falsely perceive a specifically timed pattern of stress – caused by alternating between low and mildly increased sodium levels – as a massive, continuously increasing ramp of stress. In response, the microbes end up over-responding and killing themselves. The results, Lim says, suggest a whole new way of looking at the perceptual abilities of simple cells and could even be used to develop new approaches to fighting diseases using the power of illusion.
Timing of stress response is yeast cells’ ‘Achilles heel’
“This discovery was a bit of an accident actually,” said Lim, chair of the Department of Cellular and Molecular Pharmacology at UCSF, director of the UCSF Center for Systems and Synthetic Biology, and a Howard Hughes Medical Institute (HHMI) investigator. “We were interested in the general issue of how cells interpret information over time. Frequency is a key aspect of all our communications, whether it’s hearing language or transmitting radio signals, but do cells themselves use this kind of information? It’s something we don’t know much about.”
To explore this question, two postdoctoral fellows in Lim’s lab, Ping Wei, PhD, now at Peking University School of Life Sciences, and Amir Mitchell, PhD, set up a system that allowed them to expose yeast to a mild stressor – a small increase in salt in the yeast’s environment – and to oscillate between the increased salt level and the baseline level at different frequencies.
Normally, sensor molecules in a yeast cell detect changes in salt concentration and instruct the cell to respond by producing a protective chemical. After this transient response, the cell can resume growing happily as if conditions had not changed. The researchers found that the cells were perfectly capable of adapting when they flipped the salt stress on and off every minute or every 32 minutes. But to their surprise, when they tried an eight-minute oscillation of precisely the same salt level the cells quickly stopped growing and began to die off.
“That was just a jaw-dropping moment,” said Mitchell. “These cells should be able to handle this level of osmotic stress, but at one particular frequency they just go haywire. We’d never seen anything like this before.”
Could sensory illusions be used to fight cancer?
Mitchell, who was first author on the new study, went on to inspect the cellular mechanism underlying this unexpected, frequency-dependent toxicity. Using mathematical modeling and experiments in which he tweaked the molecular wiring of the mitogen activated protein kinase (MAPK) pathway that mediates the cells’ salt-sensing system, he revealed a sensory misperception: Because of the way the MAPK pathway is set up, the cells interpret an eight-minute oscillation as an ever-increasing staircase of salt concentration. This leads to excessive activation of the cells’ protective response, and ultimately to their death (see Movie).
The Latest on: Cancer Therapeutics
via Google News
The Latest on: Cancer Therapeutics
- Former Insys Therapeutics vice president was sentenced to 33 months for pushing unnecessary opioid prescriptionson January 14, 2020 at 12:54 am
The former vice president of Insys Therapeutics, a pharmaceutical company, was sentenced to almost three years for pushing doctors to prescribe unnecessary opioids on patients, according to a press ...
- Discovery could lead to new breast cancer drugson January 13, 2020 at 11:22 pm
he has studied breast cancer for the past 15 years. One of the compounds that he and his team discovered in 2006 has been licensed to Linnaeus Therapeutics for the treatment of melanoma and other ...
- Insys Therapeutics executive sentenced to 3 years in prison for lying about opioid addictionon January 13, 2020 at 8:47 pm
A former executive of Insys Therapeutics was sentenced Monday to nearly three years in prison as part ... The defense said he deserved no more than one year since he developed Subsys after watching ...
- The North America hereditary cancer testing market is expected to reach US$ 3,247.37 Mn in 2027 from US$ 1,255.79 Mn in 2018on January 13, 2020 at 4:05 pm
The North America hereditary cancer testing market is expected to reach US$ 3,247.37 Mn in 2027 from US$ 1,255.79 Mn in 2018. This market is projected to grow at a growth rate of 11.6% from 2019-2027.
- Researchers identify new pathway as biological target for colon canceron January 13, 2020 at 10:06 am
Sam Thiagalingam, PhD, corresponding author, associate professor of biomedical genetics, medicine and pathology & laboratory medicine and pharmacology & experimental therapeutics at BUSM Previous ...
- Laryngeal Cancer Therapeutics Market: Key Trends, Forecasts & Research Report 2019-2025on January 13, 2020 at 9:50 am
A recent report published by Infinium Global Research on laryngeal cancer therapeutics market provides an in-depth analysis of segments and sub-segments in the global as well as regional laryngeal ...
- TIO Bioventures Launches Treadwell Therapeutics, Seeded With $27m to Develop First-in-Class Oral Medicines Against Novel Targetson January 13, 2020 at 7:00 am
NEW YORK--(BUSINESS WIRE)--TIO Bioventures, an emerging life science venture creation fund with a mission to build companies with innovative anti-cancer therapies, today announced the launch of ...
- Editas teams up with Sandhill Therapeutics in cancer; shares up 2% premarketon January 13, 2020 at 6:14 am
Editas Medicine (NASDAQ:EDIT) perks up 2% premarket on light volume in reaction to its agreement with Sandhill Therapeutics aimed at discovering, developing and manufacturing allogeneic engineered ...
- BRIEF-Editas Medicine And Sandhill Therapeutics Collaborate To Develop Engineered Cell Medicines To Treat Canceron January 13, 2020 at 5:57 am
* EDITAS MEDICINE AND SANDHILL THERAPEUTICS, INC. ANNOUNCE COLLABORATION TO DEVELOP ENGINEERED CELL MEDICINES TO TREAT CANCER * EDITAS MEDICINE- SANDHILL WILL RECEIVE UPFRONT PAYMENT, DEVELOPMENT, ...
- Nektar Therapeutics, Bristol-Myers Expand Effort to Develop Treatment for Canceron January 10, 2020 at 10:04 am
Nektar Therapeutics shares leap as the company and Bristol-Myers said they would expand their partnership to develop a cancer treatment. That treatment is Nektar’s bempegaldesleukin (bempeg) plus ...
via Bing News