Daily Archives: 20 Feb 2021

Astronomy

Starry Night Or Black Holes? (Astronomy)

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Durham University astronomers have helped make a huge map of the night sky showing more than 25,000 active supermassive black holes in distant galaxies.

The map is the largest and sharpest ever created at ultra-low radio frequencies.

Starry night

At first glance it looks like a picture of a starry night sky, but instead what you are really seeing are supermassive black holes that emit radio waves at ultra-low frequencies.

The black holes have been captured by LOFAR, currently the world’s largest radio telescope operating at lowest frequencies.

Scientists used supercomputers to correct for the interference to LOFAR’s radio waves caused by the Earth’s ionosphere to create their map.

Durham is part of the international team involved in LOFAR.

Astronomers will use the map to discover celestial objects that only emit ultra-low frequency radio waves.

Exoplanets

These objects include diffuse matter in the large-scale structure of the universe, exoplanets whose magnetic fields are interacting with host stars, and fading jets of plasma being ejected from supermassive black holes.

Even though it is among the largest of its kind, the published map only shows two percent of the sky.

Scientists plan to continue the search for exotic phenomena like black holes for several years until a map of the entire northern sky is completed.

Find out more

Featured image: Astronomers have mapped more than 25,000 active supermassive black holes in distant galaxies © Durham University

Provided by Durham University

Astronomy

How We Can Observe Another Universe Through A Wormhole? (Astronomy)

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Summary:

○ Alexander Shatskiy considered a technique of calculating deflection of the light passing through wormholes (from one universe to another). He found fundamental and characteristic features of electromagnetic radiation passing through the wormholes.

○ He showed that the distortion of the light rays that had passed through the WH throat is caused not only by redistributing of the star density, but also by changes in their apparent brightness.

○ He also implied that if angular resolution of the observer’s instrument in our Universe is high enough, he will be able to discover the changing star density in the throat J(h).

○ He also showed that the apparent brightness of the WH’s part inside its throat does not depend on impact parameter.

Alexander Shatskiy considered a technique of calculating deflection of the light passing through wormholes (from one universe to another). He found fundamental and characteristic features of electromagnetic radiation passing through the wormholes. Making use of this, he proposed new methods of observing distinctive differences between wormholes and other objects as well as methods of determining characteristic parameters for different wormhole models.

By modifying Einstein equations, he first obtained the explicit analytical form of the solution to the first order in the small correction δ ( being defined by the equation-of-state of the matter in the WH) and then transcendental equation yielding the throat radius.

In order to know, what causes the distortion of light in wormhole, he considered that the other universe contain N stars with equal luminosities and supposed N >>> 1.

Then he assumed that, all the stars are homogeneously distributed over the celestial sphere in the other universe. An observer in our Universe who is looking at the stars in the other universe through the WH throat sees them inhomogeneously distributed over the throat. This is because of the fact that the WH throat refracts and distorts the light of these stars. The distortion will obviously be spherically symmetric with the throat center being the symmetry center.

Later, he assumed that the observer look only at the fraction of the stars seen in the thin ring with the center coinciding with the throat center, the ring radius being h and its width – dh. Hence, the observer surveys the solid angle dΩ of the other universe and, moreover, dΩ = 2π|sin θ| dθ. Here, θ(h) is the deflection angle of light rays passing through the WH throat measured relative to the rectilinear propagation (By convention, the rectilinear propagation means the trajectory passing through the center of the WH throat) . Since the total solid angle equals 4π, the observer can see dN = N dΩ/(4π) stars in the ring (Since the light deflection angle θ can exceed π, the total solid angle turns out to be more than 4π. This change, however, reduces to another constant (instead of 4π) and does not affect the final result.). Furthermore, the apparent density of the stars (per unit area of the ring dS = 2πh dh) is J = dN/dS. He, therefore, obtain:

Equation 1

The dependance θ(h),

Equation 2

where, the notations η ≡ 1/x and h˜ ≡ h/q were used. This yields

Equation 3

Taking advantage of all these formulae, they found the expression for the apparent density of the stars J(h) in the wormhole.

He noted that, 2nd formula/equation also gives the maximum possible impact parameter h = hmax which still allows the observer to see the stars of the other universe. This parameter corresponds to a zero of the second factor in the radicand in (2). Namely, hmax is equal to the least possible value of the function e^–φ / η. Having conducted trivial inquiry, he obtained:

as δ → 0.

What all these equations actually showed that the distortion of the light rays that had passed through the WH throat is caused not only by redistributing of the star density, but also by changes in their apparent brightness. Namely, as the impact parameter h increases the stellar brightness changes. This is because of the fact that as the radius h of the ring, through which the star light passes, increases, an element of the solid angle where this light scatters changes as well. The respective change in the stellar brightness is proportional to the quantity κ = dS/dΩ. Therefore, the total brightness of all the stars seen on unit area of the above-mentioned ring is dN · κ/dS.

Thus, he obtained that as N → ∞ the apparent brightness of the WH’s part inside its throat does not depend on impact parameter and, regardless of which WH model he used, the WH looks like a homogeneous spot in every wavelength range.

In spite the result obtained stating that the light distribution in the WH throat is homogeneous for each WH model, he also noted that in the real universe the number of visible stars is finite, though big. This implies that if angular resolution of the observer’s instrument in our Universe is high enough, he will be able to discover the changing star density in the throat J(h).

The left panel of Fig. 1 shows this plot for δ = 0.001. Sharp minima on the plot correspond to zeros of the sine in equation 1. This is because at sufficiently large impact parameters the light rays are deflected by large angles (θ > π) so that in the vicinities of the points θ = πn abrupt declines in distribution arise. But near these declines the observed stellar brightness tends to infinity (lensing), which ultimately provides the (on average) uniform light flow over the WH throat (see the right panel of Fig. 1).

FIG. 1: The left panel is the apparent image of the sky of the other universe as being seen through the WH throat as Nstars = 40 000. The middle panel shows the appropriate dependance J(h) when h ∈ (0, hmax) and δ = 0.1. The right panel is the apparent image of the sky of the other universe at Nstars → ∞ © Alexander Shatskiy

Positions of the declines depend on the value of δ. Hence, registering them makes it possible to determine the equation-of-state parameters of the WH matter and features of the WH model (which is highly analogous to processing the light spectra).

Reference: Alexander Shatskiy, “Image of another universe being observed through a wormhole throat”, Astronomical Journal, pp. 1-6, 2012. https://arxiv.org/abs/0809.0362

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Material science

Move Over Heavy Goggles, Here Come the Ultra-high Refractive Index Lenses (Material Science)

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POSTECH professor Junsuk Rho’s research team develops a transparent silicon without visible light loss by controlling the silicon atomic structure.

A POSTECH research team has developed a transparent amorphous silicon that transmits visible light – which permits us to distinguish the colors of objects – enabling the development of paper-thin lenses usable in head-mounted displays (HMD) that show virtual and augmented reality images in real time.

A research team – led by Professor Junsuk Rho of POSTECH’s mechanical engineering and chemical engineering departments, and Ph.D. candidate Younghwan Yang and Dr. Gwanho Yoon of the Department of Mechanical Engineering – has developed visibly transparent amorphous silicon by improving the plasma enhanced chemical vapor deposition (PECVD) method, a practice widely used by Korean display manufacturers. The researchers also succeeded in effectively controlling the light in the visible region using the newly developed silicon. This research was recently published in Advanced Materials, the most respected international journal on materials science.

© POSTECH

Since light bends more with higher refractive index, a material with high refractive index is essential in designing devices for virtual and augmented reality. However, most highly refractive materials tend to absorb light and when used in a device that produces an image by controlling the light – such as an ultra-thin lens or a hologram – their performance deteriorates. The optical materials presented so far have high transmittance with low refractive index, or, conversely, high refractive index and low transmittance, thereby limiting the production of lightweight and highly efficient optical devices.

To this, the research team utilized the PECVD method, a common technique to develop the amorphous silicon. While depositing the silicon using the PECVD method, the team explored each parameter of the process, such as temperature, pressure, plasma power, and hydrogen ratio, and uncovered the effect of each variable on the intermolecular bonds.

© POSTECH

Moreover, the team discovered a method to increase the regularity between silicon atoms by inserting hydrogen atoms between strained silicon atomic bonds, and through this, the atomic structure of amorphous silicon that possesses a high refractive index and significant transmittance was identified. In addition, the researchers succeeded in steering red, green, and blue lights in the desired direction, which could not be controlled with the conventional silicon before.

Transparent amorphous silicon has the advantage of producing hologram devices or ultra-thin lenses that are one thousandth of the thickness of conventional lenses at a fraction of the cost. The applicability of the silicon has also been expanded in that the amorphous silicon, which has been used only in thermal infrared cameras, can now be used as an optical device in the visible light region.

“The discovery of an optical element capable of controlling all visible light has revealed clues about the relationship between the atomic bonding structure and the visible light region, which has not been of interest until now,” explained Professor Junsuk Rho, the corresponding author who led the study. “As we can produce optical devices that can control all colors at low cost, we are now one step closer to commercializing virtual and augmented reality and hologram technologies only seen in movies.”

This research was conducted with the grant from the Samsung Research Funding & Incubation Center for Future Technology, the Mid-career Researcher Program, the Global Frontier Program, the Regional Leading Research Center program, and the Future Materials Discovery Project of the Ministry of Science and ICT, a fellowship from the Hyundai Motors Chung Mong-Koo Foundation, and the Next Generation Researchers Initiative of the National Research Foundation of Korea.

Featured image credit: POSTECH

Reference: Younghwan Yang, Gwanho Yoon, Sunghak Park, Seok Daniel Namgung, Trevon Badloe, Ki Tae Nam, Junsuk Rho. Revealing Structural Disorder in Hydrogenated Amorphous Silicon for a Low‐Loss Photonic Platform at Visible Frequencies. Advanced Materials, 2021; 2005893 DOI: 10.1002/adma.202005893

Provided by POSTECH

Chemistry

Selective Concentration of Cationic Species (Chemistry)

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POSTECH Professor Geunbae Lim Develops a Multiscale-Porous Anion Exchange Membrane

Sample pretreatment processes such as concentration or classification are essential to finding trace substances present in a fluid. In scientific communities recently, prolific research is being conducted on sample pretreatment techniques utilizing electrokinetics.*1 However, due to the lack of commercial anion-permselective material – an essential component – its potential application is limited to only negatively charged particles. To this, a research team at POSTECH has found a way to isolate and concentrate only the cationic samples.

A POSTECH research team led by Professor Geunbae Lim, Ph.D. candidate Minsoo Lee, and Dr. Hyukjin J. Kwon of the Department of Mechanical Engineering developed a novel type of multiscale-porous anion exchange membrane (MP-AEM) and successfully fabricated a convenient cation-permselective electrokinetic concentrator. Recognized for their excellence, these research findings were recently published as the cover paper in Advanced Functional Materials.

© POSTECH

The ion exchange material serves to induce a strong electric field region in the channel through which the fluid flows by selectively passing ions of a specific polarity. Through this, charged particles present in the fluid are continuously concentrated by receiving electric repulsion force. In general, the polarity of the ion exchange material required differs depending on the polarity of the charged particles to be concentrated. A cation exchange material is required for negatively charged species, and an anion exchange material is required for positively charged species. However, unlike the cation exchange material that currently exists, there is no material that can be easily applied to the anion exchange material, complicating the fabrication of a cation concentrator.

To this, the research team successfully produced an anion exchange material that has a MP-AEM structure with excellent mechanical strength, ion exchange capacity, and fluid transport capacity through the simple casting and salt leaching method*2 using the conventional anionic exchange materials.

The MP-AEM can be easily inserted into the electrokinetic concentrator using its peculiar property that allows simultaneous ion and fluid transport, successfully fulfilling the role of an anion exchange material. Accordingly, the research team was able to fabricate the cation-selective electrokinetic concentrator through a simple insertion and assembly method, which greatly streamlines the manufacturing process compared to the conventional method.

“The MP-AEM will play a major role in the vitalization and advancement of research fields involving cationic species,” commented Professor Geunbae Lim. He excitedly added, “Considering the high scalability of the novel exchange membrane, it will be applicable to the areas of pollution control, resource recovery, and semiconductor cleaning as well as in the fields of diagnosis and detection of diseases.”

This research was conducted with the support from the Mid-career Researcher Program of the National Research Foundation of the Ministry of Science and ICT of Korea.
 

1. Electrokinetics
A field of study dealing with the movement of charged particles in a fluid to which an electric field is applied, and the interaction between charged particles and the fluid surrounding them.

2. Salt leaching technique
A method of forming micropores in a structure by adding fine-sized salt particles in the process of casting a specific material and leaching the salt particles after the casting process.

Featured image credit: POSTECH

Reference: Minsoo Lee, Hyukjin J. Kwon, Geunbae Lim. A Multiscale‐Porous Anion Exchange Membrane for Convenient and Scalable Electrokinetic Concentration of Cationic Species. Advanced Functional Materials, 2020; 31 (5): 2006768 DOI: 10.1002/adfm.202006768

Provided by POSTECH

PHYSICS

Spin Hall Effect of Light with Near 100% Efficiency (Physics)

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POSTECH-KAIST joint research team develops perfect SHEL using anisotropic metasurfaces

A POSTECH-KAIST joint research team has successfully developed a technique to reach near-unity efficiency of SHEL by using an artificially-designed metasurface.

Professor Junsuk Rho of POSTECH’s departments of mechanical engineering and chemical engineering, and Ph.D. candidate Minkyung Kim and Dr. Dasol Lee of Department of Mechanical Engineering in collaboration with Professor Bumki Min and Hyukjoon Cho of the Department of Mechanical Engineering at KAIST have together proposed a technique to enhance the SHEL with near 100% efficiency using an anisotropic metasurface. For this, the joint research team designed a metasurface that transmits most light of one polarization and reflects the light from the other, verifying that the SHEL occurs in high-frequency region. These research findings were recently published in the February issue of Laser and Photonics Reviews, an authoritative journal in optics.

The spin hall effect of light (SHEL) refers to a transverse and spin-dependent shift of light to the plane of incidence when it is reflected or refracted at an optical interface. When amplified, it can shift light that is several times or tens of times greater than its wavelength.

Previous studies of enhancing the SHEL have involved greater light movement with little consideration for efficiency. Since enhancing the SHEL produces extremely low efficiency, studies on achieving a large SHEL and high efficiency simultaneously have never been reported.

To this, the joint research team used an anisotropic metasurface to enhance the SHEL. It was designed to enable high SHEL by transmitting most of the light from one polarization while reflecting the light from the other. By measuring the transmission of metasurface in the high-frequency region – such as microwaves – and verifying the polarization state of the transmitted light, the researchers verified the occurrence of SHEL reaching 100% efficiency.

“The very mechanisms that enhance the SHEL in most previous studies in fact lowered its efficiency,” remarked Professor Junsuk Rho, the corresponding author who led the study. “This research is significant in that it is the first study to propose a method to calculate the efficiency of the SHEL, and to increase its efficiency and enhance the SHEL simultaneously.” He added, “The SHEL is applicable in microscopic optical devices, such as beam splitters, filters and switches, and this study will improve their effectiveness.”

This research was conducted with the support from the Mid-career Researcher Program, Global Frontier Program, and Regional Leading Research Center (RLRC) Program of the Ministry of Science and ICT of Korea, and the Global-Ph.D. Fellowship of the Korean Ministry of Education.

Reference: Kim, M., Lee, D., Cho, H., Min, B., Rho, J., Spin Hall Effect of Light with Near‐Unity Efficiency in the Microwave. Laser & Photonics Reviews 2021, 15, 2000393. https://onlinelibrary.wiley.com/doi/10.1002/lpor.202000393 https://doi.org/10.1002/lpor.202000393

Provided by POSTECH

Psychology

Boys Who Play Video Games Have Lower Depression Risk (Psychology)

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Boys who regularly play video games at age 11 are less likely to develop depressive symptoms three years later, finds a new study led by a UCL researcher.

The study, published in Psychological Medicine, also found that girls who spend more time on social media appear to develop more depressive symptoms.

Taken together, the findings demonstrate how different types of screen time can positively or negatively influence young people’s mental health, and may also impact boys and girls differently.

Lead author, PhD student Aaron Kandola (UCL Psychiatry) said: “Screens allow us to engage in a wide range of activities. Guidelines and recommendations about screen time should be based on our understanding of how these different activities might influence mental health and whether that influence is meaningful.

“While we cannot confirm whether playing video games actually improves mental health, it didn’t appear harmful in our study and may have some benefits. Particularly during the pandemic, video games have been an important social platform for young people.

“We need to reduce how much time children – and adults – spend sitting down, for their physical and mental health, but that doesn’t mean that screen use is inherently harmful.”

Kandola previously led studies finding that sedentary behaviour (sitting still) appeared to increase the risk of depression and anxiety in adolescents.* To gain more insight into what drives that relationship, he and colleagues chose to investigate screen time as it is responsible for much of sedentary behaviour in adolescents. Other studies have found mixed results, and many did not differentiate between different types of screen time, compare between genders, or follow such a large group of young people over multiple years.

The research team from UCL, Karolinska Institutet (Sweden) and the Baker Heart and Diabetes Institute (Australia) reviewed data from 11,341 adolescents who are part of the Millennium Cohort Study, a nationally representative sample of young people who have been involved in research since they were born in the UK in 2000–2002.

The study participants had all answered questions about their time spent on social media, playing video games, or using the internet, at age 11, and also answered questions about depressive symptoms, such as low mood, loss of pleasure and poor concentration, at age 14. The clinical questionnaire measures depressive symptoms and their severity on a spectrum, rather than providing a clinical diagnosis.

In the analysis, the research team accounted for other factors that might have explained the results, such as socioeconomic status, physical activity levels, reports of bullying, and prior emotional symptoms.

The researchers found that boys who played video games most days had 24% fewer depressive symptoms, three years later, than boys who played video games less than once a month, although this effect was only significant among boys with low physical activity levels, and was not found among girls. The researchers say this might suggest that less active boys could derive more enjoyment and social interaction from video games.

While their study cannot confirm if the relationship is causal, the researchers say there are some positive aspects of video games which could support mental health, such as problem-solving, and social, cooperative and engaging elements.

There may also be other explanations for the link between video games and depression, such as differences in social contact or parenting styles, which the researchers did not have data for. They also did not have data on hours of screen time per day, so they cannot confirm whether multiple hours of screen time each day could impact depression risks.

The researchers found that girls (but not boys) who used social media most days at age 11 had 13% more depressive symptoms three years later than those who used social media less than once a month, although they did not find an association for more moderate use of social media. Other studies have previously found similar trends, and researchers have suggested that frequent social media use could increase feelings of social isolation.

Screen use patterns between boys and girls may have influenced the findings, as boys in the study played video games more often than girls and used social media less frequently.

The researchers did not find clear associations between general internet use and depressive symptoms in either gender.

Senior author Dr Mats Hallgren (Karolinska Institutet) has conducted other studies in adults finding that mentally-active types of screen time, such as playing video games or working at a computer, might not affect depression risk in the way that more passive forms of screen time appear to do.

He said: “The relationship between screen time and mental health is complex, and we still need more research to help understand it. Any initiatives to reduce young people’s screen time should be targeted and nuanced. Our research points to possible benefits of screen time; however, we should still encourage young people to be physically active and to break up extended periods of sitting with light physical activity.”

Featured image: Video gaming. Credit: ulricaloeb on Flickr (CC BY 2.0)

Reference: Kandola, A., Owen, N., Dunstan, D., & Hallgren, M. (2021). Prospective relationships of adolescents’ screen-based sedentary behaviour with depressive symptoms: The Millennium Cohort Study. Psychological Medicine, 1-9. doi: 10.1017/S0033291721000258

Provided by UCL

Medicine

Spina Bifida Can be Caused by Uninherited Genetic Mutations (Medicine)

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Genetic mutations which occur naturally during the earliest stages of an embryo’s development can cause the severe birth defect spina bifida, finds a new experimental study in mice led by UCL scientists.

The study, published in Nature Communications, explains for the first time how a ‘mosaic mutation’ – a mutation which is not inherited from either parent (either via sperm or egg cell) but occurs randomly during cell divisions in the developing embryo – causes spina bifida.

Specifically the scientists, based at UCL Great Ormond Street Institute of Child Health, found that when a mutation in the gene Vangl2 (which contains information needed to create spinal cord tissue) was present in 16% of developing spinal cord cells of mouse embryos, this was sufficient to produce spina bifida.

Researchers say the findings add to scientists’ understanding of how and why mosaic mutations can affect and disrupt cell function, including those of neighbouring cells, helping cause birth defects.

For parents, the findings may help reduce the burden felt by those who believe their child inherited spina bifida from them via genes, and believe future children could also inherit the condition. This is often discussed during genetic counselling.

Spina bifida and current knowledge

Spina bifida is one of a group of birth defects called neural tube defects, affecting the brain or spinal cord. They happen in the first month of pregnancy, often before a woman even knows that she is pregnant. People born with this condition suffer nerve damage because part of their spinal cord remains exposed while in the womb. Advances in recent years now allow surgeons in a few centres around the world, including at Great Ormond Street Hospital and University College London Hospital, to perform surgery on foetuses in the womb to reduce the neurological consequences of their condition*.

Some neural tube defects can be prevented by taking folic acid supplements before and during early pregnancy, yet these conditions continue to affect around one in every thousand pregnancies globally. Researchers say they do not fully understand why mosaic mutations occur – though environmental factors may be involved – and cannot yet draw a link with taking (or not) folic acid during pregnancy. Notwithstanding this they say folic acid is known to help embryonic cells make DNA and encourage all expectant mothers to add folic acid to their diets from before conception.

Commenting on the potential causes, Principle Investigator, Dr Gabriel Galea (UCL Great Ormond Street Institute of Child Health), said: “Some environmental factors are known to increase the risk of these conditions occurring and very few affected individuals or their parents receive a meaningful genetic diagnosis. The discovery that mosaic mutations, which cause spina bifida, may not be inherited from either parent, and are not necessarily present in blood or saliva commonly used for genetic testing, may explain why.”

Genetic mutations

Genetic mutations happen in every cell throughout development. In order to grow from a fertilised egg cell into a foetus, each of our cells must replicate and divide in order to increase in number and grow. Cells must copy their DNA every time they divide, but mistakes can happen which change the DNA sequence in the daughter cells. These DNA code mistakes, called mutations, are then inherited by all cells derived from that cell. If these mutations happen in germ cells – the egg and sperm cells – they are inherited from parent to offspring. Many mutations do not happen in germ cells, but rather in cells which give rise to specific tissue types. These are known as mosaic mutations.

Experimental study approach

In humans with spina bifida a number of gene mutations have been identified, but in many cases it had not been known whether they could cause spina bifida.

In this experimental study, researchers caused a specific mutation, which inactivates a single gene called Vangl2 in mouse embryos. This gene is part of a cellular signalling pathway which tells cells which way they are facing within a tissue. Mutations in this pathway had been identified in people who have neural tube defects, and recent reports from the USA and China previously found mosaic Vangl2­-pathway mutations in 15% of human foetuses with spina bifida. For the cellular signalling pathway to function normally, cells must interact with their neighbours in order to communicate directional information.

For the study, researchers induced this mutation of Vangl2 in a small proportion of cells which form the developing spinal cord of mice. This was done in a number of mouse embryos. Researchers then counted the proportion of spinal cells which harboured this mutation in those which had successfully covered their spinal cord with skin (ie had developed normally), versus those which had an exposed spinal cord (had spina bifida).

Researchers found that when the mutated Vangl2 gene was present in just 16% of developing spinal cord cells, spina bifida occurred.

They say, these results show that the cellular signalling process is surprisingly vulnerable to the uninheritable mosaic mutations. Each mutant cell stops each of its neighbouring cells from functioning to promote spinal cord development. And each cell has six neighbouring cells on average, massively amplifying the effects of each mutant cell.

Explaining the findings, Dr Galea, a Wellcome Clinical Research Career Development Fellow, said: “We found that the requirement for cells to talk to each other makes them exquisitely vulnerable to mutations in the signalling pathway that Vangl2 acts in. We now need to understand whether this vulnerability extends to other genes which could cause spina bifida. Detecting these mosaic mutations in living people will require technological advances and careful analysis of tissues resected during surgery.”

* A team from UCL, UCLH and GOSH has operated on the abnormally developed spinal cords of two babies in the womb, in a medical first for the UK (October 2018)

Featured image: Advanced microscopy image of developing spinal cord ©UCL

Reference: Galea, G.L., Maniou, E., Edwards, T.J. et al. Cell non-autonomy amplifies disruption of neurulation by mosaic Vangl2 deletion in mice. Nat Commun 12, 1159 (2021). https://www.nature.com/articles/s41467-021-21372-4 https://doi.org/10.1038/s41467-021-21372-4

Provided by UCL

Biology

New Technology Enables Predictive Design of Engineered Human Cells (Biology)

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Capability could accelerate the development of new treatments for diseases

Northwestern University synthetic biologist Joshua Leonard used to build devices when he was a child using electronic kits. Now he and his team have developed a design-driven process that uses parts from a very different kind of toolkit to build complex genetic circuits for cellular engineering.

One of the most exciting frontiers in medicine is the use of living cells as therapies. Using this approach to treat cancer, for example, many patients have been cured of previously untreatable disease. These advances employ the approaches of synthetic biology, a growing field that blends tools and concepts from biology and engineering.

The new Northwestern technology uses computational modeling to more efficiently identify useful genetic designs before building them in the lab. Faced with myriad possibilities, modeling points researchers to designs that offer real opportunity.

“To engineer a cell, we first encode a desired biological function in a piece of DNA, and that DNA program is then delivered to a human cell to guide its execution of the desired function, such as activating a gene only in response to certain signals in the cell’s environment,” Leonard said. He led a team of researchers from Northwestern in collaboration with Neda Bagheri from the University of Washington for this study.

Leonard is an associate professor of chemical and biological engineering in the McCormick School of Engineering and a leading faculty member within Northwestern’s Center for Synthetic Biology. His lab is focused on using this kind of programming capability to build therapies such as engineered cells that activate the immune system, to treat cancer.

Bagheri is an associate professor of biology and chemical engineering and a Washington Research Foundation Investigator at the University of Washington Seattle. Her lab uses computational models to better understand — and subsequently control — cell decisions. Leonard and Bagheri co-advised Joseph Muldoon, a recent doctoral student and the paper’s first author.

“Model-guided design has been explored in cell types such as bacteria and yeast, but this approach is relatively new in mammalian cells,” Muldoon said.

The study, in which dozens of genetic circuits were designed and tested, will be published Feb. 19 in the journal Science Advances. Like other synthetic biology technologies, a key feature of this approach is that it is intended to be readily adopted by other bioengineering groups.

To date, it remains difficult and time-consuming to develop genetic programs when relying upon trial and error. It is also challenging to implement biological functions beyond relatively simple ones. The research team used a “toolkit” of genetic parts invented in Leonard’s lab and paired these parts with computational tools for simulating many potential genetic programs before conducting experiments. They found that a wide variety of genetic programs, each of which carries out a desired and useful function in a human cell, can be constructed such that each program works as predicted. Not only that, but the designs worked the first time.

“In my experience, nothing works like that in science; nothing works the first time. We usually spend a lot of time debugging and refining any new genetic design before it works as desired,” Leonard said. “If each design works as expected, we are no longer limited to building by trial and error. Instead, we can spend our time evaluating ideas that might be useful in order to hone in on the really great ideas.”

“Robust representative models can have disruptive scientific and translational impact,” Bagheri added. “This development is just the tip of the iceberg.”

The genetic circuits developed and implemented in this study are also more complex than the previous state of the art. This advance creates the opportunity to engineer cells to perform more sophisticated functions and to make therapies safer and more effective.

“With this new capability, we have taken a big step in being able to truly engineer biology,” Leonard said.

The research was supported by the National Institute of Biomedical Imaging and Bioengineering (award number 1R01EB026510), the National Institute of General Medical Sciences (award number T32GM008152) and the National Cancer Institute (award number F30CA203325).

The title of the paper is “Model-guided design of mammalian genetic programs.”

Featured image: Synthetic biologists achieve a breakthrough in the design of living cells © Justin Muir

Provided by Northwestern University

Medicine

Big Causes of Heart Failure in COVID-19 Patients Include Obesity, Hypertension (Medicine)

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Poor heart health may be key driver for worsening rates of heart failure during pandemic

Key contributors of heart failure in COVID-19 patients will likely be due to pre-existing risk factors, such as obesity and hypertension, that portend worse outcomes with the virus, reports a new Northwestern Medicine Viewpoint.

Currently, a leading concern is that the virus directly attacks the heart leading to inflammation or myocarditis with the potential to cause lasting damage to the heart muscle, the authors said. 

“But that direct attack to the heart, or myocarditis, causing clinically significant heart dysfunction and heart failure has only been observed in a minority of people infected with COVID-19,” said senior study author Dr. Sadiya Khan, assistant professor of preventive medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine cardiologist. “What remains unclear is if findings of myocarditis on imaging tests with minimal or without symptoms will have long-lasting health effects.” 

The paper synthesized data from six papers investigating the relationship between COVID-19 and heart effects.

The paper was published today, Sept. 30, in the Journal of the American Medical Association.

“I want to reframe the discussion to the bigger burden of poor heart health, which affects far more people with COVID-19,” Khan said. “People with obesity or hypertension are more likely to get COVID-19, are more likely to have a severe case and are more likely to have cardiovascular complications even without direct heart injury or myocarditis.”

“It may be the virus amplifies the poor heart health that already exists and was worsening in the U.S. population,” Khan said. “It is known the virus can prompt the release of inflammatory molecules throughout the body. This may affect the heart indirectly, especially in people with risk factors, like obesity and hypertension. These people are already at risk for heart failure, especially heart failure with preserved ejection fraction, the most common type of heart failure today.”

Some health experts have warned that exercising might be dangerous for former COVID-19 patients who developed myocarditis. 

“We don’t want to see people at low risk stop exercising out of fear,” Khan said. “We’ve already seen the collateral damage of the pandemic leading to avoidance of hospitals for patients who may be experiencing heart attacks or strokes.”

Patients who had COVID-19 will need to be monitored long term for symptoms of heart failure, said first author Dr. Priya Mehta Freaney, cardiovascular disease fellow at Northwestern Medicine. “This is especially critical for those who experienced lung injury and may have cardiovascular complications related to chronic pulmonary disease following recovery from COVID-19,” she noted. 

“The pandemic emphasizes once again, the urgency with which we need to change how we are approaching overall health,” Khan said. “Before the pandemic even started, we have been seeing worsening trends with higher numbers of people, especially under age 65 years dying from heart failure. We are losing ground in the battle against heart failure, in large part, due to growing rates of obesity and diabetes and poor control of high blood pressure. And the disparities in heart failure are clear and have been amplified during COVID-19.”

Reference: Priya Mehta Freaney, Sanjiv J. Shah, Sadiya S. Khan et al., “COVID-19 and Heart Failure With Preserved Ejection Fraction”, JAMA. 2020;324(15):1499-1500. doi: 10.1001/jama.2020.17445

Provided by Northwestern University