Common bacteria on verge of becoming antibiotic-resistant superbugs

Antibiotic resistance is poised to spread globally among bacteria frequently implicated in respiratory and urinary infections in hospital settings, according to new research at Washington University School of Medicine in St. Louis.

Bacteria that cause many hospital-associated infections are ready to quickly share genes that allow them to resist powerful antibiotics. The illustration, based on electron micrographs and created by the Centers for Disease Control and Prevention, shows one of these antibiotic-resistant bacteria.

The study shows that two genes that confer resistance against a particularly strong class of antibiotics can be shared easily among a family of bacteria responsible for a significant portion of hospital-associated infections.
Drug-resistant germs in the same family of bacteria recently infected several patients at two Los Angeles hospitals. The infections have been linked to medical scopes believed to have been contaminated with bacteria that can resist carbapenems, potent antibiotics that are supposed to be used only in gravely ill patients or those infected by resistant bacteria.
"Carbapenems are one of our last resorts for treating bacterial infections, what we use when nothing else works," said senior author Gautam Dantas, PhD, associate professor of pathology and immunology. "Given what we know now, I don't think it's overstating the case to say that for certain types of infections, we may be looking at the start of the post-antibiotic era, a time when most of the antibiotics we rely on to treat bacterial infections are no longer effective."
Dantas and other experts recommend strictly limiting the usage of carbapenems to cases in which no other treatments can help.
The study, conducted by researchers at Washington University, Barnes-Jewish Hospital and the National University of Sciences and Technology in Pakistan, is available online in Emerging Infectious Diseases.
The researchers studied a family of bacteria called Enterobacteriaceae, which includes E. coli, Klebsiella pneumoniae and Enterobacter. Some strains of these bacteria do not cause illness and can help keep the body healthy. But in people with weakened immune systems, infections with carbapenem-resistant versions of these bacteria can be deadly.
The Centers for Disease Control and Prevention named carbapenem-resistant Enterobacteriaceae as one of the three most urgent threats among emerging forms of antibiotic-resistant disease. Studies have shown the fatality rate for these infections is above 50 percent in patients with weakened immune systems.
Two genes are primarily responsible for carbapenem-resistant versions of these disease-causing bacteria. One gene, KPC, was detected in New York in 2001 and quickly spread around most of the world, with the exception of India, Pakistan and other South Asian countries. This gene was present in the bacteria that recently contaminated medical equipment in a Los Angeles hospital where two patients died.
A second carbapenem resistance gene, NDM-1, was identified in 2006 in New Delhi, India. It was soon detected throughout South Asia, and most patients infected by bacteria with NDM-1 have had an epidemiological link to South Asian countries.
Dantas and his collaborators were curious about why the two resistance genes seemed to be geographically exclusive. For the study, they compared the genomes of carbapenem-resistant bacteria isolated in the United States with those of carbapenem-resistant bacteria isolated in Pakistan.
Based on the apparent geographic exclusivity of the two resistance genes, the scientists expected to find that bacteria from the two regions were genetically different. Such differences could explain why the two resistance genes weren't intermingling. But the researchers' results showed otherwise. The bacteria's high genetic similarity suggests that the antibiotic resistance genes could be shared easily between bacteria from the two geographic regions.
The researchers also sequenced a special portion of bacterial genetic material called plasmids. Most of a bacteria's DNA is found in its chromosome, but bacteria also have many extra, smaller and circular bits of DNA known as plasmids that easily can pass from one bacterial strain to another. A plasmid is like a bacterial gene delivery truck; it is the primary way antibiotic resistance genes spread between bacteria.
The researchers identified a few key instances in which the plasmids carrying NDM-1 or KPC were nearly identical, meaning they easily could facilitate the spread of antibiotic resistance between disease-causing bacteria found in the United States and South Asia. Recent evidence suggests that this intermingling already may be happening in parts of China.
"Our findings also suggest it's going to get easier for strains of these bacteria that are not yet resistant to pick up a gene that lets them survive carbapenem treatment," Dantas said. "Typically, that's not going to be a problem for most of us, but as drug-resistant forms of Enterobacteriaceae become more widespread, the odds will increase that we'll pass one of these superbugs on to a friend with a weakened immune system who can really be hurt by them."
 

Journal Reference:

1. Mitchell W. Pesesky, Tahir Hussain, Meghan Wallace, Bin Wang, Saadia Andleeb, Carey-Ann D. Burnham, Gautam Dantas. KPC and NDM-1 Genes in RelatedEnterobacteriaceaeStrains and Plasmids from Pakistan and the United States. Emerging Infectious Diseases, 2015; 21 (6) DOI: 10.3201/eid2106.141504

Courtesy: ScienceDaily
 

Researchers solve science behind scalp cooling and the reasons for hair loss in cancer treatment

Hair loss is one of the most distressing side-effects of cancer treatment and can even deter some patients from undergoing life-saving chemotherapy. But researchers at the University of Huddersfield are establishing the scientific basis for a rapidly-advancing scalp cooling technology that can ensure hair retention in a vast number of cases.

There is also an added benefit that the increased positivity of patients who retain their hair can help to boost their immune systems and therefore aid recovery.
Experienced cancer researcher Dr Nikolaos Georgopoulos heads the project and the other key figure is Omar Hussain. With an academic background in the pharmacology of cancer treatment, he has been working closely with the Huddersfield firm Paxman Coolers Ltd, an innovator in the field of scalp cooling and which is now the world's leading supplier of hair-loss prevention systems. Its scalp coolers have been used by more than 100,000 patients in 32 countries.
Omar has recently completed his two-year position as the associate in a UK government-backed Knowledge Transfer Partnership (KTP) formed between Paxman and the University of Huddersfield. Now he has embarked on a programme of doctoral research supervised by Dr Georgopoulos and fully-funded by Paxman.
The PhD project will build on the findings of the research team, who have conducted laboratory experiments which provide scientific backing for clinical evidence that scalp cooling can eliminate hair loss during chemotherapy in at least 50 per cent of cases.
The effectiveness of cooling
Progress has also been made in establishing why cooling works and the researchers have also explored its effectiveness and its limitations when different combinations of drugs are used during chemotherapy. Dr Georgopoulos, Omar Hussain and their collaborators are the first to have published scientific papers which demonstrate that cooling works. They include an article in the journal Toxicology in Vitro.
The two Huddersfield scientists have also attended the recent St Gallen International Breast Cancer Conference, held in Vienna, where they gave two poster presentations on aspects of the scalp cooling research.
Dr Georgopoulos said that there was a range of explanations for the effectiveness of cooling. For example, the lowered temperature of the scalp could result in greatly reduced blood flow to the area, so that less of the drug finds its way to the hair follicles. It is also possible that cooling reduces the level of drug uptake in the region of the hair cells, or that the same effect is produced by a lowering of the metabolism.
Omar's PhD research will lead to a deeper understanding of the science behind cooling, focussing on the issues of drug uptake and drug release.
Happier patients have stronger immune systems
The University of Huddersfield researchers and the Paxman firm are aware that the benefits of scalp cooling technology can extend beyond the issue of hair loss.
Figures have shown that eight per cent of patients refuse chemotherapy because they fear losing their hair, said Omar Hussain. "So to have our research out there is a reassurance to them," he added.
Clinicians tend to regard hair loss as "collateral damage" said Dr Georgopoulos. "What they care about, of course, is saving lives. But we know the difference that keeping hair makes to patients and there is evidence that happier patients have stronger immune systems."
"Mood relates to hormonal release and that can affect the function of the immune system. Positivity can have an effect - there are scientific papers which suggest that it affects the efficacy of the treatment.
"So if you look in a mirror and feel good about yourself because you have a full head of hair, that is a big psychological boost that can help people through their treatment."
The researchers and Paxman now hope that scalp cooling will be embedded as a routine part of chemotherapy and that it will be an established element of nurse training.
The managing director of Paxman is Richard Paxman, who commented: "We are delighted with the results of the University of Huddersfield research and are extremely excited that it is being presented at this year's International Breast Cancer Conference. Every day we hear personal stories from patients and their families about the positive results of scalp cooling so it is great to see clinical evidence to back this up."
 

Journal Reference:

1. Nikolaos T. Georgopoulosa et al. Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxici. Toxicology in Vitro, Volume 28, Issue 8, December 2014, Pages 1366%u20131376

Courtesy: ScienceDaily
 

Ebola: Study announces a durable vaccine

Acytomegalovirus (CMV)-based vaccine provides long-lasting protective immunity against Ebola virus, and has potential for development as a disseminating vaccine strategy to prevent ebolavirus infection of wild African ape populations.

A new study shows the durability of a novel 'disseminating' cytomegalovirus (CMV)-based Ebola virus (Zaire ebolavirus; EBOV) vaccine strategy that may eventually have the potential to reduce ebolavirus infection in wild African ape species.
The multi-institutional study is led by Dr Michael Jarvis at Plymouth University, and is published in March 2015, in Vaccine.
African apes serve as a main source of ebolavirus transmission into the human population. As a consequence, the prevention of ebolavirus infection in African apes could reduce the incidence of future human ebolavirus outbreaks. Ebola virus is also highly lethal to African apes, and is regarded as a major threat to the survival of these populations in the wild. Such a 'disseminating' vaccine offers hope for both stabilizing these endangered ape populations and protecting humans against the devastating effects of Ebola.
The innovative approach may overcome the major hurdle to achieving high vaccine coverage of these animals. They live in of some of the most remote, inaccessible regions of the world which makes conventional, individual vaccination near impossible.
Apart from being very immunogenic (able to provoke an immune response) and species-specific, CMV can also spread easily from individual to individual, a process which remains remarkably unaffected by prior CMV immunity. This is the basis of the team's current innovative strategy of using a CMV-based ebolavirus vaccine that can spread through wild ape populations as a means to provide high levels of protective ebolavirus-specific immunity without the need for direct vaccination.
The current publication expands on a 2011 study, in which the same collaborative research team first showed the ability of a CMV-based vaccine to provide protection against Ebola virus in a mouse challenge model.
Most Ebola virus vaccine mouse studies, including this earlier 2011 study, have only assessed protection against Ebola virus infection shortly after vaccination (generally within six weeks post-vaccination). The present study showed that immunity induced by CMV is extremely long-lasting, with Ebola virus-specific immune responses being maintained for greater than 14 months (equivalent to half the life span of a mouse) following only a single dose of the vaccine.
Importantly, immunity induced by the CMV vaccine was able to provide protection against Ebola virus at least until 119 days (approximately four months) post-vaccination. Long-lasting immunity will be critical for the eventual success of this disseminating vaccine approach. It is also an attractive characteristic for a (albeit non-disseminating) CMV-based Ebola virus vaccine for direct use in humans, which is an additional area of development of the current collaborative research group.
The next step, which is nearing completion, is to trial the vaccine using CMV in the macaque EBOV challenge model (regarded as the 'gold standard' for testing vaccines in a model translatable to Ebola infection in great apes and humans). The results from this study further support the utility of this approach and will be published in the next few months. Many questions clearly remain, including the nature of the immunity conferred by disseminated CMV vaccines (in the current study mice were directly inoculated).
"We must walk before we can run, but this study provided a little skip," said Dr. Michael Jarvis, corresponding author on the study from Plymouth University Peninsula Schools of Medicine and Dentistry. "However, this disseminating approach does potentially provide a workable solution to a currently intractable problem of achieving high vaccine coverage in inaccessible ape populations. Given the impact of ebolavirus on African ape numbers in the wild, and the role of apes as a route of ebolavirus transmission to humans via the bush meat trade, such a vaccine would be a win-win for humans and wild apes alike."
To this end the project has been incorporated as a component of an international research program, which includes key players such as the World Wildlife Fund and National Institutes of Health, which are dedicated to driving the project forward to mobilization.
 

Journal Reference:

1. Michael A. Jarvis et al. A cytomegalovirus-based vaccine provides long-lasting protection against lethal Ebola virus challenge after a single dose. Vaccine, March 2015 DOI: 10.1016/j.vaccine.2015.03.029 

 Courtesy: ScienceDaily

Scientists coax stem cells to form 3-D mini lungs

Scientists have coaxed stem cells to grow the first three-dimensional mini lungs.

 

Scientists, led by the University of Michigan Medical School, coax stem cells to form mini lungs, 3-D structures that mimic human lungs and survived in the lab for 100 days.

 

Previous research has focused on deriving lung tissue from flat cell systems or growing cells onto scaffolds made from donated organs.
In a study published in the online journal eLife the multi-institution team defined the system for generating the self-organizing human lung organoids, 3D structures that mimic the structure and complexity of human lungs.
"These mini lungs can mimic the responses of real tissues and will be a good model to study how organs form, change with disease, and how they might respond to new drugs," says senior study author Jason R. Spence, Ph.D., assistant professor of internal medicine and cell and developmental biology at the University of Michigan Medical School.
The scientists succeeded in growing structures resembling both the large airways known as bronchi and small lung sacs called alveoli.
Since the mini lung structures were developed in a dish, they lack several components of the human lung, including blood vessels, which are a critical component of gas exchange during breathing.
Still, the organoids may serve as a discovery tool for researchers as they churn basic science ideas into clinical innovations. A practical solution lies in using the 3-D structures as a next step from, or complement to, animal research.
Cell behavior has traditionally been studied in the lab in 2-D situations where cells are grown in thin layers on cell-culture dishes. But most cells in the body exist in a three-dimensional environment as part of complex tissues and organs.
Researchers have been attempting to re-create these environments in the lab, successfully generating organoids that serve as models of the stomach, brain, liver and human intestine.
The advantage of growing 3-D structures of lung tissue, Spence says, is that their organization bears greater similarity to the human lung.
How to make a human lung in a dish
To make these lung organoids, researchers at the U-M's Spence Lab and colleagues from the University of California, San Francisco; Cincinnati Children's Hospital Medical Center; Seattle Children's Hospital and University of Washington, Seattle manipulated several of the signaling pathways that control the formation of organs.
First, stem cells -- the body's master cells -- were instructed to form a type of tissue called endoderm, which is found in early embryos and gives rise to the lung, liver and several other internal organs.
Scientists activated two important development pathways that are known to make endoderm form three-dimensional tissue. By inhibiting two other key development pathways at the same time, the endoderm became tissue that resembles the early lung found in embryos.
In the lab, this early lung-like tissue spontaneously formed three-dimensional spherical structures as it developed. The next challenge was to make these structures expand and develop into lung tissue. To do this, the team exposed the cells to additional proteins that are involved in lung development.
The resulting lung organoids survived in the lab for over 100 days.
"We expected different cells types to form, but their organization into structures resembling human airways was a very exciting result," says lead study author Briana Dye, a graduate student in the U-M Department of Cell and Developmental Biology.
 

Journal Reference:

1. Briana R Dye, David R Hill, Michael AH Ferguson, Yu-Hwai Tsai, Melinda S Nagy, Rachel Dyal, James M Wells, Christopher N Mayhew, Roy Nattiv, Ophir D Klein, Eric S White, Gail H Deutsch, Jason R Spence. In vitro generation of human pluripotent stem cell derived lung organoids. eLife, 2015; 4 DOI: 10.7554/eLife.05098 

Courtesy: ScienceDaily
 

Why do cells rush to heal a wound? Mysteries of wound healing unlocked

Researchers at the University of Arizona have discovered what causes and regulates collective cell migration, one of the most universal but least understood biological processes in all living organisms.

These are leader cells, shown fluorescing green in this photomicrograph, pull follower cells in their wake as they move to cover and heal a wound.

The findings, published in the March 13, 2015, edition of Nature Communications, shed light on the mechanisms of cell migration, particularly in the wound-healing process. The results represent a major advancement for regenerative medicine, in which biomedical engineers and other researchers manipulate cells' form and function to create new tissues, and even organs, to repair, restore or replace those damaged by injury or disease.
"The results significantly increase our understanding of how tissue regeneration is regulated and advance our ability to guide these processes," said Pak Kin Wong, UA associate professor of mechanical and aerospace engineering and lead investigator of the research.
"In recent years, researchers have gained a better understanding of the molecular machinery of cell migration, but not what directs it to happen in the first place," he said. "What, exactly, is orchestrating this system common to all living organisms?"
Leaders of the Pack
The answer, it turns out, involves delicate interactions between biomechanical stress, or force, which living cells exert on one another, and biochemical signaling.
The UA researchers discovered that when mechanical force disappears -- for example at a wound site where cells have been destroyed, leaving empty, cell-free space -- a protein molecule, known as DII4, coordinates nearby cells to migrate to a wound site and collectively cover it with new tissue. What's more, they found, this process causes identical cells to specialize into leader and follower cells. Researchers had previously assumed leader cells formed randomly.
Wong's team observed that when cells collectively migrate toward a wound, leader cells expressing a form of messenger RNA, or mRNA, genetic code specific to the DII4 protein emerge at the front of the pack, or migrating tip. The leader cells, in turn, send signals to follower cells, which do not express the genetic messenger. This elaborate autoregulatory system remains activated until new tissue has covered a wound.
The same migration processes for wound healing and tissue development also apply to cancer spreading, the researchers noted. The combination of mechanical force and genetic signaling stimulates cancer cells to collectively migrate and invade healthy tissue.
Biologists have known of the existence of leader cells and the DII4 protein for some years and have suspected they might be important in collective cell migration. But precisely how leader cells formed, what controlled their behavior, and their genetic makeup were all mysteries -- until now.
Broad Medical Applications
"Knowing the genetic makeup of leader cells and understanding their formation and behavior gives us the ability to alter cell migration," Wong said.
With this new knowledge, researchers can re-create, at the cellular and molecular levels, the chain of events that brings about the formation of human tissue. Bioengineers now have the information they need to direct normal cells to heal damaged tissue, or prevent cancer cells from invading healthy tissue.
The UA team's findings have major implications for people with a variety of diseases and conditions. For example, the discoveries may lead to better treatments for non-healing diabetic wounds, the No. 1 cause of lower limb amputations in the United States; for plaque buildup in arteries, a major cause of heart disease; and for slowing or even stopping the spread of cancer, which is what makes it so deadly.
The research also has the potential to speed up development of bioengineered tissues and organs that can be successfully transplanted in humans.
About the Study
In the UA Systematic Bioengineering Laboratory, which Wong directs, researchers used a combination of single-cell gene expression analysis, computational modeling and time-lapse microscopy to track leader cell formation and behavior in vitro in human breast cancer cells and in vivo in mice epithelial cells under a confocal microscope.
Their work included manipulating leader cells through pharmacological, laser and other means to see how they would react.
"Amazingly, when we directed a laser at individual leader cells and destroyed them, new ones quickly emerged at the migrating tip to take their place," said Wong, who likened the mysteries of cell migration and leader cell formation to the processes in nature that cause geese to fly in V-formation or ants to build a colony.

Journal Reference:

1. Reza Riahi, Jian Sun, Shue Wang, Min Long, Donna D. Zhang & Pak Kin Wong. Notch1–​Dll4 signalling and mechanical force regulate leader cell formation during collective cell migration. Nature Communications, March 2015 DOI: 10.1038/ncomms7556 

Courtesy: ScienceDaily

Injured spinal cord: Regeneration possible with epothilone?

Damage to the spinal cord rarely heals because the injured nerve cells fail to regenerate. The regrowth of their long nerve fibers is hindered by scar tissue and molecular processes inside the nerves. An international team of researchers led by DZNE scientists in Bonn now reports in Science that help might be on the way from an unexpected quarter: in animal studies, the cancer drug epothilone reduced the formation of scar tissue in injuries to the spinal cord and stimulated growth in damaged nerve cells. Both promoted neuronal regeneration and improved the animals' motor skills. 

Cross section rat spinal cord. Immunostaining: axons (red), synapses (green), motor neurons (blue).

Nerve cells are wire-like conductors that transmit and receive signals in the form of electrical impulses. This function can be impaired by accidents or disease. Whether or not the affected nerves can recover largely depends on their location: for instance nerve cells in the limbs, torso and nose can regenerate to some degree and regain some or all of their function.
In contrast, the neurons in the brain and spinal cord do not have this ability. If they are damaged by accident or disease, the patient is likely to suffer long-term paralysis or other disabilities. But why is regeneration of these neurons and their long nerve fibers impeded? It is already known that inhibiting factors in newly formed scar tissue and other cellular processes block axon regrowth.
Seeking the ideal treatment
"The ideal treatment for promoting axon regeneration after spinal cord injury would inhibit the formation of scar tissue," says Professor Frank Bradke, who leads a working group at the DZNE's site in Bonn and who conducted the study. "However, it is also important that the growth-inhibiting factors are neutralized while reactivating the poor axons' regenerative potential." A feasible administration of a potential treatment is also essential for clinical application.
In cooperation with international researchers, Bradke and his team have now managed to take another step towards the development of a future treatment. From their previous research, it was already known that stabilizing microtubules would reduce the formation of scar tissue and promote axonal growth. Microtubules are long, tubular filaments inside the cell that can grow and shrink dynamically. They are part of the cell's supportive skeleton, which also controls cell growth and movement.
The substance epothilone can stabilize microtubules and is already licensed on the American market -- as a cancer treatment. "It all depends on the dose," says Dr. Jörg Ruschel, the study's lead author. "In higher doses, epothilone inhibits the growth of cancer cells, while low doses have been shown to stimulate axonal growth in animals without the severe side-effects of cancer treatment." Epothilone is superior to other cancer drugs with a similar effect because it can penetrate the blood-brain barrier into the central nervous system, thus reaching the damaged axons directly.
One substance -- many effects
Experiments have shown epothilone works on several levels. Epothilone reduces the growth of scar tissue by inhibiting the formation of microtubules in the cells that form the scar tissue. Therefore they cannot migrate to the spinal cord lesion and cause wound scarring. At the same time, epothilone promotes growth and regeneration in the nerve cells by causing microtubules to grow into the damaged axon tips.
In short: through the same effect, namely microtubule stabilization, epothilone is able to inhibit directional movement in scar-forming cells while stimulating active growth in nerve cell axons. The animals treated with epothilone after spinal cord injury walked better than those that received no treatment, due to improved balance and coordination. The next goal of Bradke and his team is to test the effect of epothilone on various types of lesion.

Journal Reference:

1. Jörg Ruschel, Farida Hellal, Kevin C. Flynn, Sebastian Dupraz, David A. Elliott, Andrea Tedeschi, Margaret Bates, Christopher Sliwinski, Gary Brook, Kristina Dobrint, Michael Peitz, Oliver Brüstle, Michael D. Norenberg, Armin Blesch, Norbert Weidner, Mary Bartlett Bunge, John L. Bixby and Frank Bradke. Systemic administration of epothilone B promotes axon regeneration after spinal cord injury. Science, 2015 DOI: 10.1126/science.aaa2958 

Courtesy: ScienceDaily

Molecule-making machine simplifies complex chemistry

A new molecule-making machine could do for chemistry what 3-D printing did for engineering: Make it fast, flexible and accessible to anyone.

 

A machine in University of Illinois chemistry professor Martin Burke's lab assembles complex small molecules out of simple chemical building blocks, like a 3-D printer on the molecular level.

Chemists at the University of Illinois, led by chemistry professor and medical doctor Martin D. Burke, built the machine to assemble complex small molecules at the click of a mouse, like a 3-D printer at the molecular level. The automated process has the potential to greatly speed up and enable new drug development and other technologies that rely on small molecules.

"We wanted to take a very complex process, chemical synthesis, and make it simple," said Burke, a Howard Hughes Medical Institute Early Career Scientist. "Simplicity enables automation, which, in turn, can broadly enable discovery and bring the substantial power of making molecules to nonspecialists."

The researchers described the technology in a paper featured on the cover of the March 13 issue of Science.

"Small molecules" are a specific class of complex, compact chemical structures found throughout nature. They are very important in medicine -- most medications available now are small molecules -- as well as in biology as probes to uncover the inner workings of cells and tissues. Small molecules also are key elements in technologies like solar cells and LEDs.

However, small molecules are notoriously difficult to make in a lab. Traditionally, a highly trained chemist spends years trying to figure out how to make each one before its function can even be explored, a slowdown that hinders development of small-molecule-based medications and technologies.

"Up to now, the bottleneck has been synthesis," Burke said. "There are many areas where progress is being slowed, and many molecules that pharmaceutical companies aren't even working on, because the barrier to synthesis is so high."

The main question that Burke's group seeks to answer: How do you take something very complex and make it as simple as possible?

The group's strategy has been to break down the complex molecules into smaller building blocks that can be easily assembled. The chemical building blocks all have the same connector piece and can be stitched together with one simple reaction, the way that a child's interconnecting plastic blocks can have different shapes but all snap together. Many of the building blocks Burke's lab has developed are available commercially.

To automate the building-block assembly, Burke's group devised a simple catch-and-release method that adds one building block at a time, rinsing the excess away before adding the next one. They demonstrated that their machine could build 14 different classes of small molecules, including ones with difficult-to-manufacture ring structures, all using the same automated building-block assembly.

"Dr. Burke's research has yielded a significant advance that helps make complex small molecule synthesis more efficient, flexible and accessible," said Miles Fabian of the National Institutes of Health's National Institute of General Medical Sciences, which partially funded the research. "It is exciting to think about the impact that continued advances in these directions will have on synthetic chemistry and life science research."

The automated synthesis technology has been licensed to REVOLUTION Medicines, Inc., a company that Burke co-founded that focuses on creating new medicines based on small molecules found in nature. The company initially is focusing on anti-fungal medications, an area where Burke's research has already made strides.

"It is expected that the technology will similarly create new opportunities in other therapeutic areas as well, as the industrialization of the technology will help refine and broaden its scope and scalability," Burke said.

"Perhaps most exciting, this work has opened up an actionable roadmap to a general and automated way to make most small molecules. If that goal can be realized, it will help shift the bottleneck from synthesis to function and bring the power of making small molecules to nonspecialists."

Journal Reference:

1. Junqi Li, Steven G. Ballmer, Eric P. Gillis, Seiko Fujii, Michael J. Schmidt, Andrea M. E. Palazzolo, Jonathan W. Lehmann, Greg F. Morehouse, and Martin D. Burke. Synthesis of many different types of organic small molecules using one automated process. Science, 13 March 2015 DOI: 10.1126/science.aaa5414 

Courtesy: ScienceDaily