Biotecnika newspaper 6 february 2018 by BioTecNika

February 6th, 2018.

Vol. 02 NO 6

NEWS - PAGE 2

NEWS - PAGE 4 PROTEIN COMBO FOUND TO EXERT REGENERATING EFFECT IN PARKINSON’S

MUTATIONAL TRIGGER TO IMMUNE DISEASES IDENTIFIED

NEWS - PAGE 8

NEWS - PAGE 10 BOOSTING OESTROGEN ACTIVITY GIVES HOPE OF NEW NEUROBLASTOMA TREATMENT POSSIBILITIES

PREVIOUSLY UNKNOWN, BACTERIA-HUNTING MARINE VIRUSES DISCOVERED

BUDGET SPECIAL

PM Research Fellowship of Rs 1,800 Crore India is a country with tens of top class research institutions in the basic sciences and in the medical and engineering sciences. The combined strength of junior researchers from all these institutions will run into the ten thousands.

By Disha Padmanabha

PM Research Fellowship of Rs 1,800 Crore To be Launched | Here is What You Should Know ! Now, the Modi Administration’s 2018 budget proposal, announced with great respect to this fact has allocated Rs 1,800 crore under the Prime Minister Research Fellowship (PMRF) scheme for BTech students working towards their PhDs in premier institutes. The Centre will provide Rs.75,000 as monthly fellowship to those researchers doing their PhDs in Indian Institutes of Technology (IITs) or Indian Institute of Science (IISc). “The government has … launched a Prime Minister Research Fellows scheme this year… Under this scheme, we will identify 1,000 best B.Tech students each year from premier institutions and provide them facilities to do PhDs in the Indian Institutes of Technology (IITs) and the Indian Institute of Science (IISc)… The students will also be rewarded with a handsome fellowship amount,” Union finance minister Arun Jait-

ley said while presenting the Union Budget. The government has also taken steps to “set up a specialised railway university in Vadodara” and “two new full fledged schools of planning and architecture. Additionally, 18 School of Planning and Architecture will be set up in IITs and NITs as autonomous schools,” the central minister said. Calling the year’s budget “world’s largest healthcare program”, Mr. Jaitley has also announced extensive healthcare schemes for the vulnerable. “We are slowly progressing towards universal health coverage,” he said in his speech. Regarding the PMRF, around 1000 students will be selected every year for the fellowship for three years and the stipend of Rs.75, 000 per month will be paid for five years. The ministry will reportedly be granting scholar-

ship to 3,000 students in total. The fellowship is applicable to the students of IIT, NIT, IISc and IIIT (students from the other institutes can apply for the fellowship but will have to pursue research in IITs only). The applicants should ideally score high in their programs or courses (above 8 CGPA), have a strong academic background and should be from the above mentioned institutes. Using this attempt to woo students as a backdrop, the finance minister in his Budget 2018 presentation talked about how the PMRF will help identify bright students pursuing BTech in premiere engineering institutes and they will be provided higher-education opportunities in IITs IISc Bangalore with handsome financial assistance.

the undergraduate students in taking up research, the fellowship will also address the problem of faculty deficit. IITs are finding it difficult to have pool of good brains that will step up to the faculty in the future. Over a period of time, we will be able to build a pool of good caliber researchers and it will make a big difference on faculty recruitment.”

The development follows closely on the heels of students at IITs stopping to go abroad for higher education in large numbers as compared to trend of last few decades. They now stay back and around 10% to 15% go abroad and that too preferably for jobs rather than higher education. “So what will happen, we need to find faculty for them and research areas,” said a source from IIT Delhi to NEWS18. The source added, “The idea was proposed some time back – apart from encouraging

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Vol. 02 NO 6

February 6th, 2018.

MUTATIONAL TRIGGER TO IMMUNE DISEASES IDENTIFIED

By Disha Padmanabha

GTPase of immunity-associated protein 5 (Gimap5) is linked with lymphocyte survival, immune homeostasis, and (auto)immune disease. Gimap proteins are predominantly expressed in lymphocytes and regulate lymphocyte survival during development, selection, and homeostasis. Specifically, polymorphisms in human GIMAP5 are associated with increased risk of islet autoimmunity in type 1 diabetes (T1D), systemic lupus erythematosus (SLE), and asthma. Members of this family share a GTP-binding AIG1 homology domain and seem to be localized to different subcellular compartments, with Gimap5 localizing in multivesicular bodies (MVB) and lysosomes. Overall, a function for Gimaps in maintaining T cell homeostasis is not clearly defined. Now, an international group of scientists have discovered how a gene mutation affects T cell function to promote immune disorders and then tested a treatment based on the discovery—successfully fixing donated immune cells from a 16-year-old boy with an abnormally low level of white blood cells called lymphopenia. “Our data suggest GSK3 inhibitors will improve T-cell survival and function and may prevent or correct immune-related disorders in people with Gimap5 loss-of-function mutations,” said Dr. Hoebe, Ph.D., who is at the division of immunobiology. “Therapeutically targeting this pathway may be relevant for treating people with Gimap5 mutations linked to autoimmunity in type 1 diabetes (T1D), systemic lupus erythematosus (SLE), or asthma.” Immune system disorders lead to abnormally low immune activity (deficiency) or over-

activity (autoimmunity). Immune deficiency diseases decrease the body’s ability to fight infection, while autoimmunity prompts the body to attack its own tissues. Both are common causes of illness, and malfunctioning T cells are linked to both. Despite the critical role of Gimap5 in immune cell function, the mechanism(s) underlying its activity haven’t yet been identified. The Cincinnati team has now shown that Gimap5 is a critical inhibitor of GSK3β in both human and mouse CD4+ cells. If GSK3 isn’t inactivated—due to lack of Gimap5 function—it causes DNA damage in expanding T cells, which affects T-cell function and survival. The researchers’ studies showed that targeting GSK3β in the T cells of Gimap5-deficient mice led to improved T-cell survival, prevented liver damage and the development of colitis. “Our studies reveal a key role for Gimap5 in inactivating GSK3β during CD4+ T cell activation, a link that is critically required to maintain T cell fitness and allows for productive T cell proliferation. We propose that the Gimap5- mediated inactivation of GSK3β is an essential molecular mechanism to support productive CD4+ T cell responses.” They claim that their results point to a “remarkable therapeutic potential” for the use of GSK3 inhibitors to improve CD4+ T-cell survival and proliferation and to prevent immunopathology. GSK3 inhibitors have already been used to treat disease, including Alzheimer’s disease, mood disorder, cancer, and diabetes mellitis, they note. “Our current data reveal a new therapeutic application of GSK3 inhibitors specifically in the treatment of immu-

nodeficient patients that have GIMAP5 LOF [loss of function] mutations.…We posit that GSK3-inhibitors will improve overall T-cell survival and function and may prevent/correct immune- associated sequelae observed in these patients.” The researchers acknowledge that further

research will be needed before their findings can be translated into the clinic. Nevertheless, Hoebe says, “We believe the use of GSK3 inhibitors to prevent or correct these type of immune-related diseases holds great potential.“

This confocal microscopic image of a healthy mouse T cell uses color florescence to illustrate how the protein Gimap5 (upper-right faint-green area) and the enzyme GSK3 (red) overlap in small structures called vesicles inside cells (colocalized-yellow area). This happens before GSK3 enters the cell nucleus (shown in blue). This step is important to limit DNA damage in active T cells during their expansion. The image is part of a study published Jan. 30 by Nature Communications from researchers at Cincinnati Children’s.

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February 6th, 2018.

World’s First Ear Implants Crafted Via One’s Own Cells Using 3D Printing Chinese researchers grow new ears for five children suffering from microtia using their own cells with the help of 3D scanning and 3D printing. Microtia is a congenital malformation of the external ear, with a varied regional prevalence rate of 0.83 to 17.4 per 10,000 births worldwide, and higher prevalence rates in Hispanics and Asians. The external part of the ear or the auricle is an important identifying feature of human face, and hence its deformity has a profound effect on self-confidence and psychological development in the afflicted children. Current cosmetic procedures of treating microtia mainly include the wear of auricular prosthesis, implantation of non-absorbable auricular frame materials or an autologous rib cartilage framework. Non-absorbable frames, such as silastic or high-density polyethylene, generate an excellent ear shape without donor site morbidity, but they lack bioactivity and can lead to extrusion and infections. But now, in a work that’s the first study of its kind, Chinese scientists have engineered a patient-specific ear-shaped cartilage in vitro using a 3D printed biodegradable scaffold and Microtia Chondrocyte (MCs) cartilage cells. “We were able to successfully design, fabricate, and regenerate patient-specific external

ears,” the researchers wrote in their study, which followed each child for up to 2½ years. “Nevertheless, further efforts remain necessary to eventually translate this prototype work into routine clinical practices,” they wrote. “In the future, long-term (up to 5 years) follow-up of the cartilage properties and clinical outcomes … will be essential.” The project was started off with a scan of the healthy ear and a digital image of it created using 3DPRO software. This digital image was then symmetrically mirrored to guide reconstruction. A corresponding resin model of this mirrored ear was 3D printed on a Z Corp Spectrum 510 3D printer, a model that first shipped in 2005 by the company who would later be acquired by 3D Systems in 2012. The 3D printed model was used to cast a pair of molds from clay and silicone, which could then hold biomaterial scaffolds. To produce the biodegradable biomaterial scaffolds, a 9 square centimeter inner PCL mesh with three square milimeter grids and a thickness of 1.37 mm was 3D printed. This inner core was wrapped with PGA unwoven fibers and coated with PLA. Expanded MCs harvested from the child’s microtic ear. These were evenly dropped onto the PGA/ PLA layer of the ear-shaped scaffold and then placed in a cell culture solution. The cartilage ear was removed after twelve weeks.

Scientists Design Drug to Control Premature Differentiation of Stem Cells

“Stem cells are like flour – they can be baked into any number of things like pies, cookies or bread – but once that happens, there is no going back to flour,” says senior author Fabio Rossi, Professor of Medical Genetics at UBC’s Biomedical Research Centre and the new UBC School of Biomedical Engineering. “The problem was that all our stem cells were turning into ‘bread’ and we really needed them to stay as ‘flour’ so they could continue to replicate, creating enough cells so that we can transplant and regenerate the tissue effectively.” “Stem cells are like flour – they can be baked into any number of things like pies, cookies or bread – but once that happens, there is no going back to flour,” says senior author Fabio Rossi, Professor of Medical Genetics at UBC’s Biomedical Research Centre and the new UBC School of Biomedical Engineering. “The problem was that all our stem cells were turning into ‘bread’ and we really needed them to stay as ‘flour’ so they could continue to replicate, creating enough cells so that we can transplant and regenerate the tissue effectively.”

tein known as Setd7 that plays a role in controlling stem cell growth and their maturation into muscle fibres. Using a drug co-developed by Rossi, the researchers were able to inhibit the Setd7 protein to prevent the stem cells from differentiating so they could continue to divide. They then implanted these stem cells into the hind leg of mice affected by a mouse-model of muscular dystrophy and found that the cells fused to the muscle, regenerated the tissue and improved the strength of the muscle.

By Disha Padmanabha

The cartilage ear was surgically implanted in a similar way to rib cartilage. The child’s skin was draped over the cartilage and it fit the new shape of the ear thanks to vacuum drainage. Now, the researchers have over two years of follow-up data and the results are promising. None of the children rejected the new ears, four of the five ears developed cartilage after the implantation and though two showed slight distortion after the surgery, three were

healthily shaped. “This work clearly shows tissue engineering approaches for reconstruction of the ear and other cartilaginous tissues will become a clinical reality very soon,” Cornell University biomedical engineering Professor Lawrence Bonassar told CNN. “The aesthetics of the tissue produced are on par with what can be expected of the best clinical procedures at the present time.“

By Disha Padmanabha

L-R: Robert Judson and Fabio Rossi.

“This discovery unveils a new method to boost the therapeutic potential of muscle stem cells, allowing these cells, when transplanted into damaged tissue, to facilitate tissue regeneration and improve muscle function,” said Robert Judson, postdoctoral fellow at UBC, senior scientist at STEMCELL technologies and lead author of the paper.

The team of collaborators identified a pro-

Vol. 02 NO 6

February 6th, 2018.

Protein Combo Found to Exert Regenerating Effect in Parkinson’s Alzheimer‘s disease and Parkinson’s disease are the most common neurodegenerative diseases worldwide. Despite all the efforts made by the scientific community, current available treatments have limited effectiveness, without halting the progression of the disease. Parkinson’s is a motor neuron disorder characterised by a loss of dopaminergic neurons in the substantia nigra of the brain. These nerve cells are found in the black substance of the brain, where they produce the neurotransmitter dopamine, a key modulator of involuntary movement. Two factors; Vascular Endothelial Growth Factor (VEGF) and Glial Cell-derived Neurotrophic Factor (GDNF), are proteins that play an essential role in nerve cell function by inducing cell growth, plasticity and survival. Now, scientists at the University of the Basque Country have found that these two neurotrophic factors work in synergy to benefit patients with early-stage Parkinson’s disease. The results showed that the changes caused by the condition were not homogeneous in the different parts of the brain affected. “The impairment is correlated with the specific anatomic distribution of the dopaminergic neurons and their terminals,” pointed out the researcher Catalina Requejo.

trophic Factor (GDNF) were delivered encapsulated in microspheres or in nanospheres, even smaller than the former, comprising a biocompatible, biodegradable polymer: Poly Lactic-co-glycolic Acid (PLGA), which allows them to be released continuously and gradually. Furthermore, the factors were administered in a combined way to determine whether, together, they induced a synergistic effect. The results were encouraging in both the early and severe phase of the model. The combining of the VEGF and GDNF not only significantly reduced the degeneration of the dopaminergic neurons of the black substance, it also induced the formation of new cells and cellular differentiation. “The consequences for the dopaminergic system were even worse, which supports the beneficial synergistic effects exerted by the VEFG and the GDNF in Parkinson’s,” concluded the researcher. These Spanish researchers have opened the door on a new approach to the treatment of Parkinson’s disease, a neurodegenerative disease that, along with Alzheimers and ALS, is proving a massive challenge for biotech and pharma alike.A

By Disha Padmanabha

In the course of the study, therapeutic strategies based on the release of neurotrophic factors were applied. Since these factors encourage cell growth, plasticity and survival, they therefore play an essential role in controlling neuronal function. The Vascular Endothelial Growth Factor (VEGF) and the Glial Cell-derived Neuro-

Lysosomes and Mitochondria Catch up on Regulation in Cell In the latest scoop, scientists chanced upon the two key cellular structures, mitochondria and lysosome getting in “touch” to exchange regulatory tips with respect to their respective cellular functions. Both mitochondria and lysosomes are essential for maintaining cellular homeostasis, and dysfunction of both organelles has been observed in multiple diseases. Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network, which drives cellular metabolism. Similarly, lysosomes undergo constant dynamic regulation by the RAB7 GTPase, which cycles from an active GTP-bound state into an inactive GDP-bound state upon GTP hydrolysis. This rare discovery has implications for the research of many diseases, including Parkinson’s and cancer, as well as for the understanding of normal aging.

“In some ways, we assume that scientists have discovered all the major inner workings of our cells in the 21st century. And yet in this work, we made a new observation that these two organelles are directly talking to each other,” said principal investigator Dr. Dimitri Krainc, the Aaron Montgomery Ward Professor and chair of the Ken and Ruth Davee Department of Neurology at Northwestern University Feinberg School of Medicine. “It’s a surprising finding that provides new insights into normal cell function and will likely have implications for a number of diseases across the board.” “The discovery of these mitochondria-lysosome contacts is extremely exciting. We now show that these contacts offer a potential site through which mitochondria and lysosomes can crosstalk, and it suggests that defects in the regulation of this contact site may drive the pathogenesis [disease mecha-

By Disha Padmanabha

nisms] of various human diseases,” said first author Yvette Wong, a postdoctoral fellow in Krainc’s laboratory. Krainc’s laboratory had previously identified a functional link between mitochondrial and lysosomal dysfunction in Parkinson’s disease, but this study, however, is the first to identify direct physical contact between the two organelles. The team used video microscopy with fluorescent tagging of the two organelles, to observe that the mitochondria and lysosomes formed stable contacts inside living human cells. The authors also employed other advanced imaging techniques- including electron microscopy and super-resolution imaging- to discover that the formation and subsequent loosening of these contacts is reg-

ulated by a lysosomal protein called RAB7. The scientists are now investigating how dysfunction of the proteins that tether mitochondria and lysosomes together may affect the function of the organelles, as mutations in some of these proteins have already been implicated in neurological diseases. “It’s very important that we now know that these organelles are talking to each other directly. How exactly these contacts are disrupted in various diseases, including Parkinson’s, and how to restore them therapeutically, will be the subject of in-depth investigations in the future,” said Krainc, also director of the Center for Neurogenetics, a professor of neurological surgery and physiology at Feinberg, and a professor of neurobiology at the Weinberg College of Arts and Sciences.

Vol. 02 NO 6

February 6th, 2018.

PREVIOUSLY UNKNOWN, BACTERIA-HUNTING MARINE VIRUSES DISCOVERED

By Disha Padmanabha

“The recovery of the non-tailed autolykiviruses represents a first step in revealing extensive missed diversity in one of the two major ancient lineages of dsDNA bacterial viruses, and suggests that their ecological and evolutionary importance for microbial systems is far greater than is currently recognized,” co-senior authors Martin Polz, a civil and environmental engineering researcher at MIT, and Libusha Kelly, a systems and computational biology researcher at Albert Einstein College. By profiling tail-less, double-stranded DNA (dsDNA) viruses from bacteria in ocean samples, researchers from Massachusetts Institute of Technology and Albert Einstein College of Medicine have identified a previously unappreciated family of autolykiviruses capable of killing marine bacteria. About 10 million viruses (not all of them infect bacteria) are found in every millimeter of sea surface water, and they play a largely unsung role in the marine food chain, study lead author Kathryn Kauffman. This previously unknown, recently described virus family is particularly adept at preying on and infecting marine microbes, helping to maintain a healthy balance in ocean ecosystems. In a single day, viruses kill an estimated 20 percent of the ocean’s prolific bacteria, “releasing nutrients for survivors and re-routing the flow of materials between players and places on global scales,” Kauffman said. The team calls their discovery Autolykiviridae, after Autolykos (“the wolf itself”): a character from Greek mythology, who as a trickster and thief proved similarly tricky to

catch. But Autolykiviridae has been caught, and now that we know about it, the discovery is helping scientists to fill in a large missing link in virus evolution. The genomes of this new family are very short compared to tailed viruses, composed of about 10,000 bases, instead of the typical 40,000–50,000 for tailed viruses. The tail-less viruses look to be representatives of an ancient viral lineage defined by specific types of capsids, the protein shell that encases viral DNA — which we knew commonly infects animals and single-celled organisms, but not bacteria. “We already knew that viruses are very important there,” Kauffman says, referring to the surface ocean, where the researchers’ samples were drawn, and where about 10 million viruses are found in every milliliter of water. Polz says that while “most of the viruses studied in labs have tails, most of those in the ocean don’t.” So the team decided to study one subset of tailless viruses, which infects a group of bacteria called Vibrio. After extensive tests, they found “that some of these were infecting unusually large numbers of hosts,” he says. The team states that, typically the way researchers test for viral activity is by infecting bacteria with the viral sample and then checking the samples a day later to look for signs that patches of the bacteria have been killed off. But these particular nontailed viruses often act more slowly, and the killedoff regions don’t show up until several days have passed — so their presence was never noticed in most studies.

Another important aspect of these findings is that the Autolykiviridae were shown to be members of an ancient viral lineage that is defined by specific types of capsids, the protein shell encasing the viral DNA. Though this lineage is known to be very diverse in animals and protists — and includes viruses such as the adenoviruses that infect humans, and the giant viruses that infect algae — very few viruses of this kind have been found to infect bacteria. “This work substantially changes the existing ideas on the composition of the ocean virome by showing that the content of small, tailless viruses … is comparable to that of the tailed viruses … that are currently thought to dominate the virosphere,” says Eugene V. Koonin, a senior investigator at the National Institutes of Health, who was not involved in

this research. “This work is important also for understanding the evolution of the virus world because it shows that viruses related to the most common viruses of eukaryotes (such as adenoviruses, poxviruses, and others), at least in terms of the capsid structure, are much wider-spread in prokaryotes than previously suspected.” Koonin adds, “I further wonder whether the viruses reported here might only represent the tip of the proverbial iceberg, because capsid proteins can be highly diverged in sequence so that many are missed even in sensitive database searches. The findings are also of practical importance because the tailless viruses appear to play a major ecological role in the ocean, being responsible for a substantial fraction of bacteria-killing.”

Electron microscope images of marine bacteria infected with the non-tailed viruses studied in this research. The bacterial cell walls are seen as long double lines, and the viruses are the small round objects with dark centers. Courtesy of researchers

Vol. 02 NO 6

February 6th, 2018.

The Saviour Returns : Long-Abandoned Antibiotic Makes Come-back to Battle Superbugs Over-reliance on and misuse of antibiotics has led to warnings of a future without effective medicines. Scientists are presently searching for new drugs, antibiotics; testing microbes in sources as diverse as soil, saves and amphibian blood in addition to trying to develop new, lab-made synthetic antibiotics. All in pursuit of better new and better antibiotics. Yet, despite all these remarkable advances, we are running out of effective antibioticsthe drugs that fight infection and are essential for everything from organ transplants to the treatment of food poisoning. Therefore, scientists have now found and re-enlisted a retired antibiotic to come back and save us all. Octapeptin was discovered 40 years ago but was largely unused since, forgotten by scientists as other drugs took priority. Researchers from the University of Queensland in Australia have now re-analyzed this old and largely forgotten antibiotic and believe the drug could potentially take on resilient superbugs.

“Octapeptins were discovered in the late 1970s but were not selected for development at the time, as there was an abundance of new antibiotics with thousands of people working in antibiotic research and development,” says one of the researchers, Matt Cooper from the University of Queensland in Australia. “Given the very few researchers left in this field now, and the sparse pipeline for new antibiotics, we’ve used modern drug discovery procedures to re-evaluate its effectiveness against superbugs.” Professor Cooper said there were no new classes of antibiotics available for Gram-negative bacteria, with increasing incidence of extensive drug resistance around the world. Gram-negative bacteria are harder to kill as disease organisms, because they have an extra membrane to penetrate that is often hidden by a capsule or slime layer which acts to camouflage them from drugs and our immune system.

By Disha Padmanabha

“The emergence of resistance to meropenem, and now colistin, the antibiotic of last resort, means multi-drug and extensively drug-resistant bacteria are now a reality confronting clinicians. Octapeptin showed superior antimicrobial activity to colistin against extensively resistant Gram-negative bacteria in early pre-clinical testing. In addition, octapeptin was shown to be potentially less toxic to the kidneys than colistin” he said. Despite urgent circumstances, only one new class of antibiotic has emerged in the past 30

years. As such, the University of Queensland researchers are hoping that by re-analyzing the older antibiotic and introducing it as a superior alternative once colistin fails, they will at least have provided another weapon in our arsenal; potentially, a very powerful one. The team’s creative solution could also inspire other research that looks to repurpose old, forgotten about drugs — or even create brand new ones — that could be stockpiled for the ongoing fight against antibiotic resistance.

Mining Bitcoin from DNA : Belgian Student Earns a Bitcoin by Cracking DNA Puzzle A self-confessed “DNA Junkie”, Sander Wuyts, a Ph.D. student from the University of Antwerp (UAntwerp) and Vrije Universiteit Brussel (VUB), has won one bitcoin, worth over $10,000 by decrypting a DNA sequence. Nick Goldman is a well-known British scientist specialising in DNA and the ability to store data in it. In January 2015, the European Bioinformatics Institute professor, gave a presentation on the subject at the prestigious World Economic Forum in Davos. “DNA is a really good way of storing information,” Goldman explained. “Unlike a memory stick, for example, DNA lasts for a long time, long after the death of the ‘owner’. It’s also very compact: you can store an incredible amount of information in a minuscule space.” On the same platform, a challenge was proposed- to decode a DNA sequence in order to gain access to a key that would unlock a digital wallet, with a three-year time limit. Goldman’s challenge was set to expire on January 21, 2018. If no one had successfully sequenced a DNA sample by that time, the

Bitcoin reward would have become moot. With the deadline coming up, Goldman sent out a reminder on Twitter as no person who had obtained the tube of DNA, presumably had been able to crack the code. This tweet caught the attention of Wuyts, who requested a DNA sample from Goldman and spent the last month working with his colleagues at school to crack the code. “When I read the tweet, it goes without saying that I was extremely enthusiastic,” Wuyts wrote on his blog. “I still remember myself announcing to all of my colleagues that we should drop everything we’re doing and start solving this challenge.” Working alongside his colleagues, the computational microbiology student used the genome sequencing tools available via his university to make a play for the prize. As luck would have it, he was able to successfully decrypt the three-year old Bitcoin puzzle just five days before it was due to expire. Wuyts says that the message contained instructions on how to claim the bitcoin, a few other notes, the logo of the European Bioinformatics Institute, and a sketch of James

By Disha Padmanabha

Sander Wuyts (UAntwerp and VUB) Joyce. “To be honest, I had my doubts about the feasibility of using DNA to store data and this challenge changed that — Now I know very well that this new technology offers great opportunities, maybe even for my own future research,” Wuyts says. As for the bitcoin, Wuyts writes in his blog that he plans on holding it until the right time. “I’m probably going to sell it [the bitcoin] when the time is right and then use some of the money for my research. With the rest of

the money, I can thank the colleagues who helped me and celebrate my PhD in style,” he concludes. Meanwhile, the fact that the key was successfully decoded demonstrates how DNA storage might be used to great effect. According to Goldman, it’s a particularly safe way to store keys since not everyone has access to sequencing software — and since it takes a matter of days to read the data, it can protect investors against their tendency to sell in a panic.

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February 6th, 2018.

Crawly Caterpillar-like Bot Navigates through the Body Delivering Drugs Quirks of caterpillars and jellyfish Inspire “Millirobots” that walk, climb, jump and swim through difficult terrain in order to deliver drugs to targeted areas. We might as well one day be saying “Its time take your bots!” And I, for one, am looking forward with great enthusiasm to this day. I’d rather swallow tiny bots as opposed to those hellish, icky pills. Untethered small-scale (from several millimetres down to a few micrometres in all dimensions) robots that can non-invasively access confined, enclosed spaces may enable applications in microfactories such as the construction of tissue scaffolds by robotic assembly, in bioengineering such as single-cell manipulation and biosensing, and in healthcare such as targeted drug delivery and minimally invasive surgery. However, the existing small-scale robots have very limited mobility because they are unable to negotiate obstacles and changes in texture or material in unstructured environments. But now, a German research team has developed a robot that is about a seventh of an inch long and looks at first like no more than a tiny strip of something rubbery. Then it starts moving. The robot walks, jumps, crawls, rolls and swims. It even climbs out of

“We looked at the physical mechanism of locomotion of soft-bodied caterpillars and jellyfish and The researchers from the Stuttgart-based Max Planck Institute for Intelligent Systems found inspiration for the development of the manoeuvrability talent in nature: “When we build robots, we look at the mechanics of the movement of soft-bodied biological organisms, for example, and are inspired by them“, says Metin Sitti.”With our millirobot, the result is a mix of several soft creatures such as beetle larvae and caterpillars. However, a spermatozoid and a jellyfish also served as models.”

trasound machine, doctors can control the movement of the bot inside the human body. The magnetic microparticles that are embedded into the bot’s system allow the researchers to operate and control it using an external magnetic field. By varying the strength and direction of the magnetic field, they deform the rubber strip in different ways. This allows the millirobot to complete an obstacle course similar to what would be encountered in the human body: it can walk or roll across surfaces, jump across obstacles, crawl through narrow tubes and swim on or in liquids. In addition, it can grasp objects, transport them and deposit them at defined locations. That means the robot can potentially be deployed anywhere that physicians need to deliver a particular drug or other medical material — in the digestive tract, say, or even within the blood stream. The team tested the bot in a synthetic surgical stomach model and in chicken meat tissue, where the artificial multi-talent demonstrated excellent results. When the researchers could not observe it directly, they tracked where and how exactly the robot made his way forward using ultrasound imaging. Great challenges still need to be overcome before such a millirobot can be used in patients: for example, it needs to prove that it can be controlled within the human body. However, the researchers are confident that these hurdles can be taken.

The secret is magnetism. The millirobot, which resembles a very small rectangle of paper about four millimeters in length, is made of an elastic polymer threaded through with magnetic particles. Using existing magnetic-resonance technology, such as an ul-

With the aid of such millirobots, a surgeon would have direct access and precise control in areas of the body that can only be penetrated using a scalpel today. “Without surgery, it is currently not possible to gain access to many areas of the body. Our objective is to

the pool, moving from a watery environment into a dry one. The robot prototype is small enough to move around in a stomach or urinary system, said Metin Sitti, head of the physical intelligence department at the Max Planck Institute for Intelligent Systems in Stuttgart, Germany, who led the research team.

By Disha Padmanabha

make these regions accessible non-invasively using our soft millirobot to perform diagnosis and therapy,” says Metin Sitti. “Our objective is that our millirobot will one day transport medication to where it is needed – similar to a parcel delivery to the front door“, says Metin Sitti. “We aim to use it in minimally invasive medical procedures on the patient: either by swallowing the robot or by inserting it into the body through a small opening on the skin. From there, the robot can then move through the digestive tract or the bladder, or on to the heart – we envisage numerous possibilities.“

Panacea Biotec, Serum Institute Ink Long-Term Pacts Panacea Biotec has now announced two long term agreements with Serum Institute of India (SII) and SII’s wholly owned subsidiary, Bilthovan Biologicals B.Rajesh Jain, Panacea’s Joint Managing Director, points out that millions of children in developing countries with an annual birth of about 121 million, will get easy access to the fully liquid Hexavalent vaccine containing six important antigens to protect against six diseases – Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus influenza type B and Polio. Under the collaboration, Serum will be manufacturing and distributing the fully liquid Whole cell Pertussis (wP) and Salk-based Injectable Polio Vaccine (IPV) based Hexavalent vaccine (DTwP-HepB-Hib-IPV) developed and commercialised by Panacea Biotec, touted to be the first of its kind, a joint release said. In the next two years, both vaccine companies will together get this wP-IPV-based Hexavalent Vaccine introduced in the government’s National Immunisation Programme.

said. Adar C. Poonawalla, Serum Chief Executive and Executive Director, said the deal was “historic” since two Indian vaccine companies were collaborating to address the unmet needs of both the private and public market globally. With the convenience of ‘Six in one’, it has potential of over 250 million doses in about four years, with a market size of over $1.25 billion annually, he said.

By Disha Padmanabha

“Serum Institute of India will ensure supply of IPV bulk to Panacea Biotec, an important constituent of the Hexavalent vaccine, from its wholly owned subsidiary BBIO, a bioengineering and pharmaceutical company, registered in The Netherlands having technology and expertise for making the IPV, earlier possessed by only 3 other vaccine manufacturers in the World,” the company press release

Vol. 02 NO 6

February 6th, 2018.

Researchers Reform Flu Virus to Inhibit Pancreatic Cancer

Metastatic pancreatic ductal adenocarcinomas (PDAC) are incurable due to the rapid development of resistance to all current therapeutics. However, since oncolytic adenoviral mutants have recently emerged as a promising new strategy that negates such resistance, scientists at the Queen Mary University in London modified flu virus to block the growth of pancreatic cancer. “The new virus specifically infects and kills pancreatic cancer cells, causing few side effects in nearby healthy tissue,” said lead author, Dr Stella Man, from Barts Cancer Institute at Queen Mary University London (QMUL), who described it as “selective and effective”. “If we manage to confirm these results in human clinical trials, then this may become a promising new treatment for pancreatic cancer patients, and could be combined with existing chemotherapy drugs to kill persevering cancer cells.” The research team took advantage of a unique feature of pancreatic cancer cells – the presence of a specific molecule called alpha v beta 6 (αvβ6) on the surface. The researchers altered the flu virus in such as way that it would feature an additional small protein on its outer coat. This extra protein recognizes the αvβ6-mol-

ecules and attaches to it. Once bound, the virus enters the cell and starts to multiply. It produces copies of itself prior to bursting out of the cell and thereby destroying it in the process. The newly released viral copies can then bind onto neighboring cancer cells and repeat the same cycle, eventually removing the tumor mass altogether. The team used mice that had human pancreatic cells grafted onto them and a version of the influenza virus that had been tweaked to react to one of the unique markers of pancreatic cancer. The researchers say their new technique has produced the most selective viral cancer therapy seen to date, which allows it to be safely injected to spread around the body. Maggie Blanks, CEO of the Pancreatic Cancer Research Fund, which partly funded this research, said it was exciting to see the work coming to fruition “with such positive results”. She said: “Developing more effective treatments for pancreatic cancer becomes more urgent every year as the incidence of the disease increases, and we hope to see this research progressed further.” The team are currently seeking funding to move to clinical trials in humans in the next two years.

By Disha Padmanabha

Gene on X Chromosome Could be Reason Why Lupus Disproportionately Affects Women 9 of 10 individuals who develop lupus are women. Also, XXY individuals have increased incidence of lupus, suggesting that X chromosome dosage could be an important risk factor. Now researchers have found that the gene, TLR7, escapes silencing in lupus and may be a potent drug target for the disease. Patients of systemic lupus erythematosus (SLE), an autoimmune disease, produce antibodies to their own body tissues rather foreign proteins. The result is chronic inflammation of a few or many body tissues, including the heart, lungs, nervous system, skin, kidneys, or joints. Viruses, some medications, ultraviolet light, and specific genes are thought to contribute to development of SLE. Lupus also occurs more frequently in Japanese and Chinese populations and in blacks. The study carried out by researchers at the French National Institute of Health and Medical Research (INSERM), now demonstrates that Toll-like receptor 7 (TLR7) that is encoded from the X chromosome escapes X inactivation in B cells and myeloid cells in females and Klinefelter individuals (47,XXY). Examination of blood cells led the researchers to find that the TLR7 was then expressed

on both X chromosomes—a state called TLR biallelism—in many of the individuals’ immune cells, which made them more likely to “switch” the type of antibodies they produce. The researchers think it’s this switch that leads to a higher chance of the immune cells making antibodies that attack the body’s own tissues. A potential treatment would target TLR7 to tamp down on immune activity against normal tissues. “Currently, there is no drug that can target TLR7 in the market or used in the clinics. TLR7 is a known receptor for RNA nucleic acid which normally comes from viruses, so it is a sensor of RNA viruses, like HIV or flu virus,” said Jean-Charles Guéry, research director at the French National Institute of Health and Medical Research (INSERM), in an audio interview with Science Immunology. “As such, there is some evidence that there’s a sex bias in the susceptibility to flu virus or HIV infection.” Next up, the team plans to study TLR7 expression in women with lupus and compare their findings against the data from healthy women and men with Klinefelter syndrome.

By Disha Padmanabha

“This may lead to new information regarding the level of biallelism of TLR7 in lupus patients, and whether this could be used as

a predictive factor to predict the evolution of disease, which is currently very difficult to do,” Guéry said.

Vol. 02 NO 6

February 6th, 2018.

Biogen’s MS drug Potentiates Oncolytic Viruses In Fight Against Cancer

Oncolytic viruses are a promising anti-cancer platform, achieving significant pre-clinical and clinical milestones in recent years. They offer the attractive therapeutic combination of tumor-specific cell lysis together with immune stimulation, therefore acting as potential in situ tumor vaccines. Moreover, OVs can be engineered for optimization of tumor selectivity and enhanced immune stimulation and can be readily combined with other agents. However, these viruses need to reach tumor cells and get inside them to achieve a therapeutic effect, and this does not always happen.Now, a bunch of scientists at the Ottawa Hospital Research Institute in Canada have identified a promising solution for this problem by combining oncolytic vesicular stomatitis virus (VSV) with dimethyl fumarate, a small-molecule drug that is already in use for some nonmalignant disorders and may also have direct anticancer effects.

They have preliminary evidence that dimethyl fumarate (DMF), which is marketed by Biogen as Tecfidera to treat multiple sclerosis, boosts the potency of oncolytic viruses. In the course of their research, the team tested the effect of a DMF-VSV combo on several cancer cell lines, including renal car-

cinoma, osteosarcoma and melanoma. When they administered DMF to the renal carcinoma cells four hours prior to giving them VSV, they found the virus grew by more than 100-fold. DMF also improved the performance of herpesvirus, Sindbis and adenovirus, they report. Tecfidera’s anticancer properties have already been well documented, and the drug is currently being tested to treat chronic lymphocytic leukemia and cutaneous T cell lymphoma. The Ottawa team wanted to understand why the MS drug enhances cancer-killing viruses, so they studied gene-expression patterns on cancer cells infected with VSF, both with and without DMF and related drugs. They discovered that VSF ramps up the activity of antiviral genes—but that DMF inhibits those genes. Strong evidence that Tecfidera is safe, coupled with the availability of both marketed and investigational oncolytic viruses, should provide “a clear path toward clinical evaluation of this promising combination therapy,” the authors of the new study argued. By Disha Padmanabha

Sequenced Axolotl Genome Unravels Genetic Roots of Sophisticated Regeneration The replacement-parts king of the amphibian world, the axolotl is a fascinating creature. With extreme regeneration capabilities, these fellas are like the distant cousins of the wolverine living in a tank (with a permanent smile affixed). Once revered by Aztecs, today the axolotl appears in many forms. Native to Central Mexico, these grinning amphibians are a symbol for Mexican national identity. With big branch-like gills, lizard-like limbs, and cute perma-smile, it’s hard not to fall in love with these little critters. But then it does not just end there- in addition to being almost criminally cute, these salamanders also possess remarkable regeneration capabilities. It’s not unusual for amphibians to be able to regenerate, but axolotls take it to the next level. On top of being able to regenerate limbs, the animal can also rebuild their jaws, spines, and even brains without any scarring- making it a model of curiosity for regenerative biologists. Now, scientists in Vienna, Dresden, and Heidelberg, have for the first time, completely mapped the genome of the Mexican axolotl salamander. Despite its popularity as a biological model and use for over 150 years,

this has been difficult due to the sheer size of its genome at 32 billion base pairs. The research was part of a long-term project set out by the international group to develop a molecular toolkit for the axolotl, identifying important genes with a role in regeneration. Using this, they would be able to identify the cells that initiate regeneration and improve our understanding of the molecular mechanisms underlying it. Researchers used the PacBio-platform, a sequencing technology that produces long reads to span large repetitive regions. A total of 72.435.954 reads were sequenced. Next, Gene Myers and Siegfried Schloissnig together with colleagues developed software systems that can assemble the genome from the 72 million pieces. On analysis of the genome, the researchers found several genes unique to axolotls and other amphibians that are expressed during regeneration. Interestingly, a gene called PAX3, which was previously considered vital to the development of an organism, was completely missing from the genome. Instead, the related gene PAX7 appears to have taken over those critical functions.

By Disha Padmanabha

“Taken together, these data point to a potential role in limb regeneration for several coding and non-coding sequences that have been lost or diverged rapidly in amniotes,” senior author Eugene Myers, a researcher at the Max Planck Institute of Molecular Cell Biology and Genetics, and his colleagues wrote. “Future investigations of such sequences are likely to be a fruitful avenue for understanding the evolution of regeneration capabilities.” “We now have the map in our hands to investigate how complicated structures such as legs can be re-grown”, says Sergej Now-

oshilow, co-first author of the study. “This is a turning point for the community of scientists working with axolotl, a real milestone in a research adventure that started more than 150 years ago.” Agreeably, we’re still a long way off of being able to fully regrow missing parts but sequencing this huge genome- 10 times as large as the human genome- is a big step towards decoding how this ability can evolve and function. In the nearer future, the study may help us develop new ways to heal wounds faster to reduce recovery times and infection risks.

Vol. 02 NO 6

February 6th, 2018.

Boosting Oestrogen Activity Gives Hope of New Neuroblastoma Treatment Possibilities

By Disha Padmanabha

Sanofi Outpaces Novo, Buys Ablynx for $4.8 billion The French drugmaker has now acquired Ablynx, for $4.8 billion after the Belgian biotech turned down two previous bids by Novo Nordisk. The acquisition of Ablynx continues Sanofi’s commitment to breakthrough innovation, focused on technologies addressing multiple disease targets with single multi-specific molecules. Under the deal, Sanofi will pay 45 euros per share in cash for Ablynx, a premium of 21 percent over its closing price on Friday, and more than double the price before Novo went public with its initial bid. Nanobodies are a novel class of proprietary next generation biologicals. Ablynx is at the leading edge of Nanobody technology supporting a deep pipeline of more than 45 proprietary and partnered candidates for a wide range of therapeutic areas such as hematology, inflammation, immuno-oncology, and respiratory diseases. Eight Nanobodies have entered clinical development. Ablynx would bring to Sanofi its first-inclass acquired thrombotic thrombocytopenic purpura (aTTP) candidate caplacizumab (anti-von Willebrand factor [vWF] Nanobody), a wholly owned development program. Ablynx has already filed for approvals for caplacizumab in the European Union, with plans to do likewise in the U.S. during the first half of this year.

“With Ablynx, we continue to advance the strategic transformation of our Research and Development, expanding our late-stage pipeline and strengthening our platform for growth in rare blood disorders,” Olivier Brandicourt, Sanofi’s chief executive officer, commented. “This acquisition builds on a successful existing partnership. We are also pleased to reaffirm our commitment to Belgium, where we have invested significantly over the years in our state-of-the-art biologics manufacturing facility in Geel. We intend to maintain and support the Ablynx science center in Ghent.”

“Since our founding in 2001, our team has been focused on unlocking the power of our Nanobody technology for patients. The results of our work are validated by clinical data,” said Ablynx CEO Edwin Moses, Ph.D. “As we look ahead, we believe Sanofi’s global infrastructure, commitment to innovation, and commercial capabilities will accelerate our ability to deliver our pipeline. Our Board of Directors feels strongly that this transaction represents compelling value for shareholders and maximizes the potential of our pipeline to the benefit of all stakeholders.” By Disha Padmanabha

Vol. 02 NO 6

February 6th, 2018.

Testosterone-induced Molecule Could Explain Why Men are Better Guarded against MS

The cellular and molecular basis of sex-dimorphic autoimmune diseases, such as the CNS demyelinating disease multiple sclerosis (MS), remains unclear. Women are much more likely to develop autoimmune diseases, such as systemic lupus erythematous, rheumatoid arthritis, and multiple sclerosis. Sex hormones, including estrogen and testosterone, clearly influence disease susceptibility, but the precise cellular and molecular targets of these hormones have remained unexplained. While most studies have focused on what causes the damaging inflammation in females, there is also much to be learned by studying the factors that confer protection to males. Now however, scientists at the Northwestern University identified a testosterone-driven pathway mediated by mast cell-dependent IL-33 expression that limits the development of a destructive immune response in males; thereby specifying why men are better protected from this autoimmune disorder.

In MS, immune cells attack the myelin sheath, a membrane that wraps around the nerve axons within the brain and spinal cord. The sheath acts as insulation and assists in sending nerve signals from the brain and spinal cord to the rest of the body. The damage to the myelin sheath interrupts normal nerve signal conduction and can result in a variety of symptoms including sensory disturbances, loss of motor function and cognitive deficits. In the new Northwestern study the researchers found that, in male mice, testosterone was resulting in the production of a molecule called cytokine IL-33, which was seen to trigger a pathway that prevented the production of Th17. When the researchers treated female mice with IL-33 the damaging effect of Th17 on the myelin sheath was effectively reversed.

“This suggests a mechanism for the reduced incidence of multiple sclerosis and other autoimmune diseases in males compared to females,” said lead study author Melissa

“Because testosterone levels are seven-toeight times lower in adult women compared to men, we speculate there are insufficient levels in females to activate this protective

Brown, PhD, professor of Microbiology-Immunology. “These findings could lead to an entirely new kind of therapy for MS, which we greatly need.”

By Disha Padmanabha

pathway,” says Brown, lead author on the study. “But we showed we can activate the pathway with the guardian molecule, IL-33.” The researchers also found that women tend to develop MS at a younger age and have a relapsing-remitting course of the disease. On the other hand, men tend to develop the disease later in life and it usually worsens without a period of improvement. The timing of the disease development in men also correlates with age-related reduction of testosterone levels. The hope Northwestern researchers now have is that discovering this new specific pathway will allow more targeted therapies

to be developed. It’s also suggested that this testosterone-driven protective pathway could be a culprit in other autoimmune diseases that are seen more prominently in women over men. “Our findings have identified new and more specific cellular and molecular targets for immune intervention that we hope will lead to better therapies that leave most of the immune system intact,” Brown said. “This testosterone-driven protective pathway should also be studied in other female-biased autoimmune diseases.”

NIH Rolls Out Large-Scale Study to Evaluate HIV Treatment in Pregnant Women Perinatal HIV transmission refers to HIV transmission from mother to child during pregnancy, labor and delivery, or breastfeeding. It accounts for the majority of childhood HIV infections. Each year worldwide, an estimated 1.5 million women living with HIV give birth. Previous NIH researches have helped pave the way for development of strategies to prevent perinatal transmission both in high-resource countries like the United States and in resource-limited settings around the world. Now, the NIH has launched a large international study to compare the safety and efficacy of three antiretroviral treatment regimens for pregnant women living with HIV and the safety of these regimens for their infants. In the new study, investigators will compare the virologic efficacy of the three regimens by measuring the mother’s viral load (amount of HIV in the blood) at delivery. The study also will compare how the regimens affect rates of adverse pregnancy outcomes. “Women should have access to the best available HIV medications throughout their lives,” said Anthony S. Fauci, M.D., director of NIH’s National Institute of Allergy and Infectious Diseases (NIAID). “Our priority is to evaluate newer, improved antiretroviral

drugs during pregnancy to identify the optimal regimens for women living with HIV and their infants.” The study will focus on the current preferred first-line regimen for pregnant women recommended by the World Health Organization (WHO) and two regimens containing newer antiretroviral drugs that are becoming more widely used. It will provide data on the use of these newer drugs during pregnancy, helping to ensure that women living with HIV and their infants receive the best available treatments. The study, known as IMPAACT 2010, is a phase 3 study and will enroll 639 women who are 14 to 18 weeks pregnant, are living with HIV, and are not currently taking antiretroviral treatment. Clinical trial sites in the United States and Zimbabwe are now open for enrollment, with additional sites in Botswana, Brazil, Haiti, India, Malawi, South Africa, Tanzania, Thailand, Uganda, the United States and Zimbabwe expected to open in the coming months. The women will be randomly assigned to be administered EFV/FTC/TDF, DTG/FTC/ TAF, or DTG/FTC/TDF. Their infants will also be enrolled in the study and will receive local standard-of-care interventions for HIV

By Disha Padmanabha

prophylaxis following birth. The researchers will monitor both the women and their infants for 50 weeks after delivery, and study staff will provide the women with counseling on antiretroviral medication adherence. Researchers will also closely monitor the women’s viral loads and test the infants for HIV. If an infant becomes infected during the study, investigators will provide referrals to local sources of HIV care and treatment. Co-chair of the study Dr Shahin Lockman said: “Limited pregnancy data for newer, better antiretroviral drugs—such as DTG and TAF—can mean that pregnant women may not receive the most effective and safest medications, and can delay the general adoption of better regimens in low-resource set-

tings with high HIV prevalence. We hope that the [the trial] will provide urgently needed information regarding the safety and efficacy of these newer drugs in pregnant women and their babies, so that optimal antiretroviral regimens can be offered to pregnant women and recommended for first-line treatment of adults living with HIV throughout the world.” “Therapies for pregnant women and new mothers should be based on the best available evidence, always keeping in mind the health of the woman, her developing fetus and her newborn,” said Nahida Chakhtoura, M.D., of the Maternal and Pediatric Infectious Disease Branch at NICHD. “The results of this study will help inform optimal treatment of pregnant women living with HIV in both resource-limited and well-resourced settings.”

Vol. 02 NO 6

February 6th, 2018.

Study Uses HiPSCs to Demonstrate Contribution of Molecular Switches in Disease Risk Scientists at the Wellcome Sanger Institute and their collaborators, have now uncovered the contribution of molecular switches of genes in disease risk. The study demonstrates, for the first time, how immune cells created from human induced pluripotent stem cells (HiPSCs) can model immune response variation between people. “We have found that the impact of genetic variants on how people’s immune cells respond to a pathogen like Salmonella are condition-specific – they are only visible at certain stages of infection. This means that the effects of genetic differences in immune disorders could be missed in research, if scientists aren’t studying both the genes and their control regions, the regulatory elements, of immune cells at all stages of an infection,” said Dr Daniel Gaffney, Group Leader and senior author from the Wellcome Sanger Institute. “A benefit of using stem cells rather than pre-existing blood cells is they’re very flexible, and enabled us to study the effects of stimulation at two different levels. We analysed which genes in the genome were expressed during each stage of infection, but also looked at the activity of enhancers – the

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molecular ‘switches’ that controlled the expression of those genes. This novel combination of tools enabled us to see otherwise hidden effects of genetic variation on immune response” said Dr Kaur Alasoo, previously from the Wellcome Sanger Institute and now based at the University of Tartu, Estonia. In the course of the investigation, the team differentiated human iPSCs into macrophages that were then studied in four different states: unstimulated, after 18 hours of stimulation with a signaling molecule interferon-gamma, after five hours infection with Salmonella, and after interferon-gamma stimulation followed by Salmonella infection. They discovered that genetic variation impacts on the readiness of the immune cells to tackle an infection. They found that in particular, some individuals’ immune cells were ready to deal with the Salmonella infection, whereas other individuals’ macrophages were less ready and took longer to respond. This level of ‘readiness’ was due to a phenomenon known as enhancer priming, where some of the switches were already turned on in the unstimulated cells to facilitate a quicker response. In some cases, the immune cells could be overly eager and this can lead to an inflammatory response associated with im-

By Disha Padmanabha

Macrophages before (left) and after (right) stimulation. Credit: Kaur Alasoo, University of Tartu mune disorders. The researchers said their results “illustrate how pre-existing genetic effects on chromatin propagate to gene expression during im-

mune activation, and highlights the relevance of these hidden genetic effects for deciphering the molecular architecture of disease-associated variants.”