Lifeboat Foundation

Genetic perturbations that affect bacterial resistance to antibiotics have been characterized genome-wide, but how do such perturbations interact with subsequent evolutionary adaptation to the drug? Here, we show that strong epistasis between resistance mutations and systematically identified genes can be exploited to control spontaneous resistance evolution. We evolved hundreds of Escherichia coli K-12 mutant populations in parallel, using a robotic platform that tightly controls population size and selection pressure. We find a global diminishing-returns epistasis pattern: strains that are initially more sensitive generally undergo larger resistance gains. However, some gene deletion strains deviate from this general trend and curtail the evolvability of resistance, including deletions of genes for membrane transport, LPS biosynthesis, and chaperones. Deletions of efflux pump genes force evolution on inferior mutational paths, not explored in the wild type, and some of these essentially block resistance evolution. This effect is due to strong negative epistasis with resistance mutations. The identified genes and cellular functions provide potential targets for development of adjuvants that may block spontaneous resistance evolution when combined with antibiotics.

“Despite their abundance, astrocytes have been relatively overlooked by neuroscientists,” says Mirko Santello, last author of the study. Yet these cells are extremely important to clear transmitters released by neurons. In their study the researchers were able to show that in familial migraine the astrocytes cannot remove excessive transmitters released by neurons. “The impairment in astrocytic glutamate uptake in the cingulate cortex strongly enhances cortical dendritic excitability and thus enhances firing of the neurons,” Santello says…

Migraine is a complicated disorder that affects part of the nervous system. “Our results provide a clear example of how astrocyte dysfunction produced by a genetic defect affects neuronal activity and sensitivity to head pain triggers,” explains Mirko Santello. The findings help to better understand migraine pathophysiology and suggest that the cingulate cortex may represent a critical hub in the disease. The demonstration of the link between dysfunction of astrocytes in the cingulate cortex and familial migraine could help in devising new migraine treatment strategies.

Neuroscientists of the University of Zurich shed a new light on the mechanisms responsible for familial migraine: They show that a genetic dysfunction in specific brain cells of the cingulate cortex area strongly influences head pain occurrence.

Automated tabletop machine could accelerate the development of novel drugs to treat cancer and other diseases.

Many proteins are useful as drugs for disorders such as diabetes, cancer, and arthritis. Synthesizing artificial versions of these proteins is a time-consuming process that requires genetically engineering microbes or other cells to produce the desired protein.

MIT chemists have devised a protocol to dramatically reduce the amount of time required to generate synthetic proteins. Their tabletop automated flow synthesis machine can string together hundreds of amino acids, the building blocks of proteins, within hours. The researchers believe their new technology could speed up the manufacturing of on-demand therapies and the development of new drugs, and allow scientists to design artificial proteins by incorporating amino acids that don’t exist in cells.

Former astronaut Jeffrey Hoffman: For the long-term survival of our species, we have to become a multi-planet being.

With our rising planet’s population competing for space and resources, some people are convinced we need to look beyond Earth to help ensure humanity’s survival. As Elon Musk, the entrepreneur behind space tourism company SpaceX told Aeon’s Ross Andersen: “I think there is a strong argument for making life multi-planetary in order to safeguard the existence of humanity in the event that something catastrophic were to happen.”

Continue reading “We must become a multi-planet species” »

The role genetics and gut bacteria play in human health has long been a fruitful source of scientific enquiry, but new research marks a significant step forward in unraveling this complex relationship. Its findings could transform our understanding and treatment of all manner of common diseases, including obesity, irritable bowel syndrome, and Alzheimer’s disease.

The international study, led by the University of Bristol and published today in Nature Microbiology, found specific changes in DNA — the chains of molecules comprising our genetic make-up — affected both the existence and amount of particular bacteria in the gut.

Lead author Dr David Hughes, Senior Research Associate in Applied Genetic Epidemiology, said: “Our findings represent a significant breakthrough in understanding how genetic variation affects gut bacteria. Moreover, it marks major progress in our ability to know whether changes in our gut bacteria actually cause, or are a consequence of, human disease.”

A newly discovered Alzheimer’s gene may drive the first appearance of amyloid plaques in the brain, according to a study led by researchers at Columbia University Irving Medical Center.

Some variants of the gene, RBFOX1, appear to increase the concentration of protein fragments that make up these plaques and may contribute to the breakdown of critical connections between neurons, another early sign of the disease.

The finding could lead to new therapies that prevent Alzheimer’s and better ways of identifying people with the greatest risk of developing the disease.

One of the world’s greatest anti-aging scientists continues his groundbreaking efforts. In the photo next to Dr David Sinclair, there is a fella who kind of looks like my friend, Dr Yuancheng Ryan Lu. Is that you? (Dr Lu has confirmed that he is indeed the scientist on the right. Dr Sinclair is on the left.)

I can’t wait to see what they develop next!

Harvard scientist David Sinclair is one of Longevity’s big hitters. Just a year after raising $50M in Series B financing, his company Life Biosciences LLC is looking for $100M to progress its anti-aging research [1].

Continue reading “David Sinclair seeks £100m for anti-aging fight” »

A new experiment suggests DNA and RNA may have formed together before the origin of life.

By Valentina Lagomarsino figures by Sean Wilson

Nearly four months ago, Chinese researcher He Jiankui announced that he had edited the genes of twin babies with CRISPR. CRISPR, also known as CRISPR/Cas9, can be thought of as “genetic scissors” that can be programmed to edit DNA in any cell. Last year, scientists used CRISPR to cure dogs of Duchenne muscular dystrophy. This was a huge step forward for gene therapies, as the potential of CRISPR to treat otherwise incurable diseases seemed possible. However, a global community of scientists believe it is premature to use CRISPR in human babies because of inadequate scientific review and a lack of international consensus regarding the ethics of when and how this technology should be used.

Early regulation of gene-editing technology.