Institute for Animal Health

Newbury, United Kingdom

Institute for Animal Health

Newbury, United Kingdom
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Bovine mastitis remains the most common and costly disease of dairy cattle worldwide. A complementary control measure to herd hygiene and vaccine development would be to selectively breed cattle with greater resistance to mammary infection. Toll-like receptor 1 (TLR1) has an integral role for the initiation and regulation of the immune response to microbial pathogens, and has been linked to numerous inflammatory diseases. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) within the bovine TLR1 gene (boTLR1) are associated with clinical mastitis (CM).Selected boTLR1 SNPs were analysed within a Holstein Friesian herd. Significant associations were found for the tagging SNP -79 T > G and the 3'UTR SNP +2463 C > T. We observed favourable linkage of reduced CM with increased milk fat and protein, indicating selection for these markers would not be detrimental to milk quality. Furthermore, we present evidence that some of these boTLR1 SNPs underpin functional variation in bovine TLR1. Animals with the GG genotype (from the tag SNP -79 T > G) had significantly lower boTLR1 expression in milk somatic cells when compared with TT or TG animals. In addition, stimulation of leucocytes from GG animals with the TLR1-ligand Pam3csk4 resulted in significantly lower levels of CXCL8 mRNA and protein.SNPs in boTLR1 were significantly associated with CM. In addition we have identified a bovine population with impaired boTLR1 expression and function. This may have additional implications for animal health and warrants further investigation to determine the suitability of identified SNPs as markers for disease susceptibility.


News Article | December 5, 2016
Site: www.eurekalert.org

Just like workers in a factory, enzymes can create a final product more efficiently if they are stuck together in one place and pass the raw material from enzyme to enzyme, assembly line-style. That's according to scientists at Cornell's Baker Institute for Animal Health, the first team to recreate a 10-step biological pathway with all the enzymes tethered to nanoparticles. They were inspired to study how nanoparticles could gain biological functions through the enzymes that drive sperm tails, which turn sugar into lactate and energy so quickly that sperm can speed along at five body lengths per second. "Sperm have a highly efficient energy-producing system," said the study's lead author, Chinatsu Mukai, a postdoctoral research associate. In the Baker Institute laboratory of Alex Travis, associate professor of reproductive biology, Mukai and others had been studying metabolism and sperm function. Travis had the idea to mimic the way sperm tail enzymes are attached to a solid support in an attempt to achieve the same sort of efficiency on small man-made devices. The study was supported by a Pioneer Grant from the National Institutes of Health and published in the journal Angewandte Chemie Nov. 30. In most cells, the majority of enzymes that carry out the process of turning sugar into energy, called glycolysis, are floating around, picking up the molecules they work on as they happen along. But in sperm, the enzymes that carry out glycolysis have special regions that attach the enzymes to a solid protein scaffold that lies just beneath the membrane covering the cell and runs most of the length of the tail. "Sugar comes in through the membrane, hits the enzymes immediately underneath, and then is processed and passed down the line, giving energy production in a high-throughput fashion," said Travis. The system Mukai, Travis and their team developed works in much the same way: The sugar molecule is processed from start to finish by enzymes attached to nanoparticles. Compared with enzymes floating free in solution, the tethered enzyme system processed glucose to the end product, lactate, more efficiently, leaving lower concentrations of intermediate products than the free-floating enzyme system. Getting a 10-step pathway to function with all the components tethered is an exponential increase over previous studies, which reported a maximum of two to three steps. If the work can be enhanced to be a net producer of energy, there could be a number of practical applications, Travis said. In sperm, the energy is used for swimming and the signaling that allows it to fertilize an egg, but in nanobiotechnology, the energy could be used to power devices that carry out a variety of jobs. "Imagine devices the size of blood cells, each holding a chemotherapy drug. If outfitted with this kind of engine, then the devices could make their own energy from sugar in the bloodstream. Using molecular pumps powered by that energy, the devices could kick out that drug cargo at defined rates, and specifically where it's needed, such as at the site of a solid tumor," said Travis. His team has already applied the concept of tethered enzymes in a device to detect signs of stroke or traumatic brain injury in blood samples, a technology that he and his lab are planning to commercialize. It may even represent a step closer to realizing the potential of artificial cells, said Mukai. "You can't make an artificial cell without metabolic pathways, so this is progress in that direction," she said.


News Article | December 11, 2015
Site: www.treehugger.com

After decades of trying to solve this puzzle (since the mid-1970s), teams from the Cornell University and Smithsonian Institution have finally figured out how to make canine in-vitro fertilization (IVF) work. In the photo above are the world's first litter of IVF puppies. So cute! But why is this breakthrough important? It's not like there's a shortage of fertile dogs out there... One potential use for this technique is the preservation of endangered canid species. “We can freeze and bank sperm, and use it for artificial insemination,” said Alex Travis, associate professor of reproductive biology at the Baker Institute for Animal Health in Cornell’s College of Veterinary Medicine. “We can also freeze oocytes [eggs], but in the absence of in vitro fertilization, we couldn’t use them. Now we can use this technique to conserve the genetics of endangered species.” Thanks to IVF, very rare, almost extinct species, could be born from more common dog species, potentially bringing them back from the brink of disappearance. This IVF advance could also be useful to help rid dogs of some genetic diseases (and possibly humans, indirectly, since dogs share more than 350 similar heritable disorders and traits with humans, almost twice the number as any other species). For example, Golden Retrievers are more susceptible to lymphoma, a type of cancer, something that could potentially be cured.


News Article | December 10, 2015
Site: news.yahoo.com

Puppies from the first litter born through in vitro fertilization. A new study by Cornell University scientists opens the door for conserving endangered species and for eradicating heritable diseases in dogs. More The first-ever litter of puppies conceived through in vitro fertilization was born recently, unlocking a reproductive secret in domestic dogs that has helped researchers solve a decades-old canine biology puzzle. The findings, published online today (Dec. 9) in the journal PLOS ONE, outline the eggs-ceptional process that produced seven healthy puppies — five with two beagle parents and two with a cocker spaniel father and a beagle mother — born by scheduled caesarian section to a host female dog. In vitro ("outside the body") fertilization, also known as IVF, combines the egg and sperm in an artificial environment, creating an embryo that is then implanted in a host that carries it to full term. [See Photos: Fertility Egg-speriments Yield Litter of Playful Pups] IVF has been successfully practiced for decades, with the first IVF rabbits born in the 1950s and the first human "test tube baby," Louise Brown, born in 1978 in the United Kingdom. By the 1980s, IVF in domestic cattle produced "tens of thousands of pregnancies and offspring," according to a study published in the Journal of In Vitro Fertilization and Embryo Transfer in 1987. But decade after decade, IVF success in dogs remained elusive, primarily because when it comes to reproduction, dogs are weirder than you might expect. "In reproduction, dogs are very different from all other mammals," Alex Travis, co-author of the study and an associate professor at the Baker Institute for Animal Health at Cornell University College of Veterinary Medicine, told Live Science. Dogs only come into heat once or twice a year, which creates unique scheduling challenges for scientists studying fertilization and pregnancy. But, Travis added, there's another peculiar detail that's exclusive to canine reproduction — when a female dog ovulates, the resulting egg isn't exactly ready to be fertilized right away. In most mammals, an egg enters the fallopian tubes primed for fertilizing. Female dogs, however, produce immature eggs that must hang around in their oviducts for one or two days before they're viable, Travis said. Giving the immature eggs — or ovocytes — the extra time they needed to mature was one of the keys to the team's eventual IVF success, he added. [First Puppy Litter Born by In Vitro Fertilization | Video] But successful fertilization eluded the researchers even when they allowed for extra maturation time. Travis suspected that the sperm in their IVF equation was the culprit. He told Live Science that they went "back to the drawing board" to look at the first papers on IVF in dogs, and to take a closer look at their findings about sperm. Magnesium turned out to be a crucial missing ingredient. An early study, Travis said, reported that magnesium prevented sperm's heads and tails from developing in the way that they needed in order to penetrate an egg. Researchers from that study recommended omitting magnesium from IVF's chemical marinade. But the Cornell scientists found that conclusion to be only partly correct. While magnesium halted the sperm's progress when development happened "spontaneously," outside the oviducts, the researchers found that adding magnesium actually stimulated the sperm once their development was already underway, which typically happens when sperm interacts with the scrum of cells surrounding an egg, Travis said. And that combination did the trick, raising the fertilization rate to "80 to 90 percent," Travis said in a statement. Once the researchers had the embryos, the final step was to freeze them, in preparation for implanting them in the host dog during the proper stage of her cycle. Going to the dogs While the successful birth is cause enough for excitement, additional prospects promise other applications for IVF in domestic dogs. Combined with gene editing, IVF could mean a brighter future for breeds that suffer from inherited diseases, allowing scientists to nip genetic defects in the bud, prepping generations of embryos to develop disease free, the study authors suggest. The study could even inform future studies of genetic diseases in humans. Dogs share more than 350 hereditary traits and diseases with humans, "almost twice as many as any other species," Travis told Live Science. "Doing these things in dogs is a way to improve dog health, but also a way to test things out before you try it in a person. That’s one of the real values of the dog as the model," he added.


News Article | December 9, 2015
Site: phys.org

The breakthrough, described in a study to be published online Dec. 9 in the journal PLoS ONE, opens the door for conserving endangered canid species, using gene-editing technologies to eradicate heritable diseases in dogs and for study of genetic diseases. Canines share more than 350 similar heritable disorders and traits with humans, almost twice the number as any other species. Nineteen embryos were transferred to the host female dog, who gave birth to seven healthy puppies, two from a beagle mother and a cocker spaniel father, and five from two pairings of beagle fathers and mothers. "Since the mid-1970s, people have been trying to do this in a dog and have been unsuccessful," said Alex Travis, associate professor of reproductive biology in the Baker Institute for Animal Health in Cornell's College of Veterinary Medicine. Jennifer Nagashima, a graduate student in Travis' lab and the first to enroll in the Joint Graduate Training Program between the Smithsonian Conservation Biology Institute and Cornell's Atkinson Center for a Sustainable Future, is the paper's first author. For successful in vitro fertilization, researchers must fertilize a mature egg with a sperm in a lab, to produce an embryo. They must then return the embryo into a host female at the right time in her reproductive cycle. The first challenge was to collect mature eggs from the female oviduct. The researchers first tried to use eggs that were in the same stage of cell maturation as other animals, but since dogs' reproductive cycles differ from other mammals, those eggs failed to fertilize. Through experimentation, Nagashima and colleagues found if they left the egg in the oviduct one more day, the eggs reached a stage where fertilization was greatly improved. The second challenge was that the female tract prepares sperm for fertilization, requiring researchers to simulate those conditions in the lab. Nagashima and Skylar Sylveste, found that by adding magnesium to the cell culture, it properly prepared the sperm. "We made those two changes, and now we achieve success in fertilization rates at 80 to 90 percent," Travis said. The final challenge for the researchers was freezing the embryos. Travis and colleagues delivered Klondike, the first puppy born from a frozen embryo in the Western Hemisphere in 2013. Freezing the embryos allowed the researchers to insert them into the recipient's oviducts (called Fallopian tubes in humans) at the right time in her reproductive cycle, which occurs only once or twice a year. The findings have wide implications for wildlife conservation because, Travis said, "We can freeze and bank sperm, and use it for artificial insemination. We can also freeze oocytes, but in the absence of in vitro fertilization, we couldn't use them. Now we can use this technique to conserve the genetics of endangered species." In vitro fertilization allows conservationists to store semen and eggs and bring their genes back into the gene pool in captive populations. In addition to endangered species, this can also be used to preserve rare breeds of show and working dogs. With new genome editing techniques, researchers may one day remove genetic diseases and traits in an embryo, ridding dogs of heritable diseases. While selecting for desired traits, inbreeding has also led to detrimental genetic baggage. Different breeds are predisposed to different diseases; Golden retrievers are likely to develop lymphoma, while Dalmatians carry a gene that predisposes them to blockage with urinary stones. "With a combination of gene editing techniques and IVF, we can potentially prevent genetic disease before it starts," Travis said. Finally, since dogs and humans share so many diseases, dogs now offer a "powerful tool for understanding the genetic basis of diseases," Travis said. Explore further: Klondike, puppy born from a frozen embryo, fetches good news for endangered animals


News Article | December 2, 2016
Site: www.cemag.us

Just like workers in a factory, enzymes can create a final product more efficiently if they are stuck together in one place and pass the raw material from enzyme to enzyme, assembly line-style. That’s according to scientists at Cornell’s Baker Institute for Animal Health, the first team to recreate a 10-step biological pathway with all the enzymes tethered to nanoparticles. They were inspired to study how nanoparticles could gain biological functions through the enzymes that drive sperm tails, which turn sugar into lactate and energy so quickly that sperm can speed along at five body lengths per second. “Sperm have a highly efficient energy-producing system,” says the study’s lead author, Chinatsu Mukai, a postdoctoral research associate. In the Baker Institute laboratory of Alex Travis, associate professor of reproductive biology, Mukai and others had been studying metabolism and sperm function. Travis had the idea to mimic the way sperm tail enzymes are attached to a solid support in an attempt to achieve the same sort of efficiency on small man-made devices. The study was supported by a Pioneer Grant from the National Institutes of Health and published in the journal Angewandte Chemie Nov. 30. In most cells, the majority of enzymes that carry out the process of turning sugar into energy, called glycolysis, are floating around, picking up the molecules they work on as they happen along. But in sperm, the enzymes that carry out glycolysis have special regions that attach the enzymes to a solid protein scaffold that lies just beneath the membrane covering the cell and runs most of the length of the tail. “Sugar comes in through the membrane, hits the enzymes immediately underneath, and then is processed and passed down the line, giving energy production in a high-throughput fashion,” says Travis. The system Mukai, Travis and their team developed works in much the same way: The sugar molecule is processed from start to finish by enzymes attached to nanoparticles. Compared with enzymes floating free in solution, the tethered enzyme system processed glucose to the end product, lactate, more efficiently, leaving lower concentrations of intermediate products than the free-floating enzyme system. Getting a 10-step pathway to function with all the components tethered is an exponential increase over previous studies, which reported a maximum of two to three steps. If the work can be enhanced to be a net producer of energy, there could be a number of practical applications, Travis said. In sperm, the energy is used for swimming and the signaling that allows it to fertilize an egg, but in nanobiotechnology, the energy could be used to power devices that carry out a variety of jobs. “Imagine devices the size of blood cells, each holding a chemotherapy drug. If outfitted with this kind of engine, then the devices could make their own energy from sugar in the bloodstream. Using molecular pumps powered by that energy, the devices could kick out that drug cargo at defined rates, and specifically where it’s needed, such as at the site of a solid tumor,” says Travis. His team has already applied the concept of tethered enzymes in a device to detect signs of stroke or traumatic brain injury in blood samples, a technology that he and his lab are planning to commercialize. It may even represent a step closer to realizing the potential of artificial cells, said Mukai. “You can’t make an artificial cell without metabolic pathways, so this is progress in that direction,” she says.


News Article | December 5, 2016
Site: www.nanotech-now.com

Abstract: Just like workers in a factory, enzymes can create a final product more efficiently if they are stuck together in one place and pass the raw material from enzyme to enzyme, assembly line-style. That's according to scientists at Cornell's Baker Institute for Animal Health, the first team to recreate a 10-step biological pathway with all the enzymes tethered to nanoparticles. They were inspired to study how nanoparticles could gain biological functions through the enzymes that drive sperm tails, which turn sugar into lactate and energy so quickly that sperm can speed along at five body lengths per second. "Sperm have a highly efficient energy-producing system," said the study's lead author, Chinatsu Mukai, a postdoctoral research associate. In the Baker Institute laboratory of Alex Travis, associate professor of reproductive biology, Mukai and others had been studying metabolism and sperm function. Travis had the idea to mimic the way sperm tail enzymes are attached to a solid support in an attempt to achieve the same sort of efficiency on small man-made devices. The study was supported by a Pioneer Grant from the National Institutes of Health and published in the journal Angewandte Chemie Nov. 30. In most cells, the majority of enzymes that carry out the process of turning sugar into energy, called glycolysis, are floating around, picking up the molecules they work on as they happen along. But in sperm, the enzymes that carry out glycolysis have special regions that attach the enzymes to a solid protein scaffold that lies just beneath the membrane covering the cell and runs most of the length of the tail. "Sugar comes in through the membrane, hits the enzymes immediately underneath, and then is processed and passed down the line, giving energy production in a high-throughput fashion," said Travis. The system Mukai, Travis and their team developed works in much the same way: The sugar molecule is processed from start to finish by enzymes attached to nanoparticles. Compared with enzymes floating free in solution, the tethered enzyme system processed glucose to the end product, lactate, more efficiently, leaving lower concentrations of intermediate products than the free-floating enzyme system. Getting a 10-step pathway to function with all the components tethered is an exponential increase over previous studies, which reported a maximum of two to three steps. If the work can be enhanced to be a net producer of energy, there could be a number of practical applications, Travis said. In sperm, the energy is used for swimming and the signaling that allows it to fertilize an egg, but in nanobiotechnology, the energy could be used to power devices that carry out a variety of jobs. "Imagine devices the size of blood cells, each holding a chemotherapy drug. If outfitted with this kind of engine, then the devices could make their own energy from sugar in the bloodstream. Using molecular pumps powered by that energy, the devices could kick out that drug cargo at defined rates, and specifically where it's needed, such as at the site of a solid tumor," said Travis. His team has already applied the concept of tethered enzymes in a device to detect signs of stroke or traumatic brain injury in blood samples, a technology that he and his lab are planning to commercialize. It may even represent a step closer to realizing the potential of artificial cells, said Mukai. "You can't make an artificial cell without metabolic pathways, so this is progress in that direction," she said. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


Patent
Institute For Animal Health | Date: 2010-09-24

The present invention provides a construct which, when expressed in a host cell, is capable of producing empty virus capsids, the construct comprising: (i) a nucleotide sequence encoding a capsid precursor protein; (ii) a nucleotide sequence encoding a protease capable of cleaving the capsid precursor protein; and (iii) a control element which controls the expression of the protease such that, when the construct is present in the host cell, the control element causes the protease to be expressed at a level sufficient to cleave the capsid precursor protein, but not sufficient to induce significant toxicity in the host cell. The invention also provides a vector and a host cell comprising such a construct and their use to generate empty virus capsids.


Patent
Institute For Animal Health | Date: 2010-04-28

The present invention provides a method of identifying an animal having a genotype associated with resistance to bacterial infection comprising the steps of: (a) providing a sample from said mammal; (b) determining the alleles at one or more markers of the SAL1 locus to identify the genotype of the marker, wherein said SAL1 locus lies between 54.0 MB to 54.8 MB of chicken Chromosome 5 or an equivalent thereof; and (c) determining whether the genotype is a genotype associated with resistance to bacterial infection.


Patent
Institute For Animal Health | Date: 2010-07-05

The present invention provides a chimaeric coronavirus S protein which is based on an S protein from a coronavirus strain with restricted tissue tropism, but which comprises at least part of the S2 subunit from a coronavirus strain with extended tissue tropism, such that a virus comprising the chimaeric S protein has extended tissue tropism. The present invention also provides a virus comprising such a chimaeric S protein.

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