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Biotechnology

“Just ask questions and go for it!”

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At dinnertime in Zaina Moussa’s childhood home, the table would be filled with an array of Moroccan and Syrian dishes, representing her parents’ different backgrounds. A mix of French, Arabic, and English words would fill the air as Moussa’s siblings chattered, waiting for their father to join them. As her diabetic father pricked his finger to check his blood sugar, she and her siblings would shout out numbers to predict the results before the monitor. 

From a young age, Moussa appreciated how accessible medical devices can empower patients. She dreamed of one day studying bioengineering to learn how to create these devices. Yet, her small high school in Lubbock, Texas, had limited engineering opportunities. When a summer engineering program at a local university opened for high-school students, Moussa jumped at the chance. Over one summer, she learned how to build an electrocardiogram out of just two pennies, shower gel, an Arduino, an LCD screen, and a speaker. “The process showed me just how accessible we can make technology to those who need it,” says Moussa.

After getting accepted to MIT, Moussa arrived to campus ready to begin pursuing her biological engineering major. However, she quickly found herself struggling to adjust to her new environment compared to her support system back home. She joined the Black Women’s Alliance (BWA), whose weekend retreat helped her build a new family on campus. “We did a lot of workshops together that made me feel part of a sense of camaraderie,” she says. “I’ve been part of the organization ever since. I love being able to support others and to feel supported by so many amazing women.”

Moussa sought out research experiences through the Undergraduate Research Opportunities Program (UROP). She toured the lab of Institute Professor Robert Langer and became interested in a project about injectable hydrogels that can facilitate polyp removal during surgery. For the next two years, Moussa worked on the project and is now an author on two published papers on hydrogels and drug delivery.

Summer research experiences in other labs gave Moussa a chance to explore additional topics in medical research. During the summer after her sophomore year, she worked alongside a physician-scientist at the Mayo Clinic in the Department of Cardiovascular Medicine and Radiology. Although she knew little at the time about machine learning, she taught herself to develop a model to diagnose early stage cardiac amyloidosis. “I try to go into things thinking ‘let’s do this,’ even if I’m scared at first,” she says, laughing. “Google has definitely been my best friend for approaching any new challenge.”

Through this experience, Moussa also became introduced to the importance of patient input throughout the technical design process. This eventually inspired Moussa to pursue a combined MD/PhD. “The physician I shadowed would really take the time with each patient to educate them about their diagnosis and options,” she says. “I realized I don’t want to do research without also knowing the patient’s perspective. Since then, I’ve been interested in an MD/PhD track to combine both of my interests.”

Understanding the person behind a medical treatment has continued to be a key interest of Moussa’s. Her favorite course, WGS.S10 (Black Feminist Health Science Studies), is about the medicalization of race and the health of marginalized groups. “It also got me thinking about how we often put the blame on the patient. For example, we’ve seen the lowest rates of Covid-19 vaccination in Black and Brown communities,” explains Moussa. “We need to look towards our institutions for why this might be, not just blame the patient for vaccine hesitancy.”

“I think that’s why the intersection of engineering and humanities is so important to bringing the human back into engineering,” she says. “We need to meld these two spheres together if we’re going to make technologies that better serve our communitites.”

Moussa also enjoys understanding people better by learning new languages. In addition to the three languages of her household, Moussa has taught herself Spanish and Portugese. She also has a minor in Japanese, which she first pursued out of her love for anime. “It’s always been about the people for me, and I find that studying languages helps open up the world. By understanding a person’s language, you can begin to better understand their values and culture,” she says.

In her free time, Moussa enjoys mentoring other pre-med students through the Minority Association of Pre-Medical Students. Whenever worried students approach her about grades, she shares the advice she has gained from self studying languages. “Learning new topics is similar to learning a new language. You can’t get embarrassed, because if do, you’re not going to learn as much,” Moussa explains. “Don’t be afraid to ask for help and try to immerse yourself in the environment of whatever you’re trying to learn.”

This fall, Moussa will begin pursuing her MD/PhD in bioengineering. She hopes to use her daily conversations with patients to create technologies that meet their needs. “I’m excited to see what the future holds and I’m very open-minded. Three years ago, I wasn’t even thinking about being a physician. It’s amazing to look back and see how much I’ve changed,” she says.

“I used to face this mental gymnastics between my different interests and cultures. I still get in my head sometimes, but for the most part, I now embrace that I am both Black and Middle Eastern. Both a physician and a scientist. That’s just me,” Moussa says.

 “My new perspective is that there’s just not enough time to be invalidating yourself or worrying what other people think. Just ask questions and go for it! You’ve got this.”

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Source: https://news.mit.edu/2021/zaina-moussa-student-0511

Biotechnology

Queen of hearts

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Amphibians and humans differ in many ways, but Laurie Boyer, a professor of biology and biological engineering at MIT, is particularly interested in one of those differences. Certain types of amphibians and fish can regenerate and heal their hearts after an injury. In contrast, human adults who have experienced trauma to the heart, such as in the case of a heart attack or exposure to certain medications, are unable to repair the damage. Often, the injured heart ends up with scar tissue that can lead to heart failure.

Recent research in this area now indicates that mice, and even humans, have some capacity for cardiac repair for a short period after birth. But after even just a few days of age, that ability starts to shut off. “The heart has very limited ability to repair itself in response to injury, disease, or aging,” Boyer says.

Alexander Auld, a postdoc in the Boyer Lab, studies the key cellular mechanisms that lead heart cells to mature and lose regenerative potential. Specifically, he’s interested in understanding how cardiomyocytes, the heart cells responsible for pumping blood, develop an ability to contract and relax repeatedly. Auld tests the function of proteins that serve as signals to assemble the cardiac muscle structure after birth. The assembly of these structures coincides with the loss of regenerative ability. 

“I’m trying to piece together: What are the different mechanisms that push cardiomyocytes to assemble their contractile apparatus and to stop dividing?” Auld says. “Solving this puzzle may have potential to stimulate regeneration in the adult heart muscle.”

“The holy grail of regenerative biology would be to stimulate your own heart cells to replenish themselves,” says Boyer, who joined the MIT faculty in 2007. “Before this approach is possible, we need to achieve a deep understanding of the fundamental processes that drive heart development.”

Boyer’s lab studies how many different signals and genes interact to affect heart development. The work will enable a better understanding of how faulty regulation can lead to disease, and may also enable new therapies for people suffering from a variety of heart conditions.

Critical connections

Recently, Boyer’s lab has been studying heart development in people with Trisomy 21, or Down syndrome. Every year, 6,000 babies born in the United States have Down syndrome. Around half have heart defects. The most common heart defect in babies with Down syndrome is a hole in the heart’s center, called an atrioventricular septal defect. It is often repaired with surgery, but the repair can cause scar tissue and cardiovascular complications.

Somatic cells are those that compose an organism’s body; they differ from sex cells, which are used for reproduction. Most people have 46 chromosomes, arranged in 23 pairs, in their body’s somatic cells. In 95 percent of cases, Down syndrome results when a person has three copies of chromosome 21 instead of two –– a total of 47 chromosomes per cell. It’s an example of aneuploidy, when a cell has an abnormal number of chromosomes. Cellular attempts to adapt to the extra chromosome can cause stress on the body’s cells, including those of the heart.

MIT’s Alana Down Syndrome Center (ADSC) brings together biologists, neuroscientists, engineers, and other experts to increase knowledge about Down syndrome. ADSC launched in early 2019, led by Angelika Amon, professor of biology and a member of the Koch Institute for Integrative Cancer Research, along with co-director Li-Huei Tsai, Picower Professor and director of the Picower Institute for Learning and Memory. Amon died at age 53 in 2020 after a battle with ovarian cancer. At MIT, Amon had studied the effects of aneuploidy on cells.

“In my many wonderful scientific and personal discussions with Angelika, who was a beacon of inspiration to me, it became clear that studying Trisomy 21 in the context of heart development could ultimately improve the lives of these individuals,” Boyer says.

Change of heart

To conduct their research, Boyer’s group uses human induced pluripotent cells (hiPSCs), obtained through somatic cell reprogramming. The revolutionary technique was developed by Sir John B. Gurdon and Shinya Yamanaka, who in 2012 won the Nobel Prize in Physiology or Medicine for their work. Reprogramming works by converting specialized, mature somatic cells with one particular function into specialized, mature, cells with a different function.

Boyer’s lab uses hiPSCs from human adults with Down syndrome and converts them into cardiomyocytes through somatic cell reprogramming. Then, they compare those cardiomyocytes with reprogrammed cells from individuals who do not have Down syndrome. This work helps them deduce why the extra chromosome in people with Down syndrome may cause congenital heart defects.

“We can now begin to pinpoint the faulty signals and genes in Trisomy 21 cardiac cells that affect heart development,” Boyer says. “And with that same idea, we can also discover how we might actually be able to ameliorate or fix these defects.”

With this technique, the team can track how aspects of a specific patient’s cell development correlate with their clinical presentation. The ability to analyze patient-specific cells also has implications for personalized medicine, Boyer says. For instance, a patient’s skin or blood cells –– which are more easily obtained –– could be converted into a highly specialized mature cell, like a cardiac muscle cell, and tested for its response to drugs that could possibly cause damage to the heart before they reach the clinic. This process can also be used to screen for new therapies that can improve the outcome for heart failure patients.

Boyer presented the group’s research on Down syndrome at the New England Down Syndrome Symposium, co-organized in November 2020 by MIT, ADSC, Massachusetts Down Syndrome Congress, and LuMind IDSC Foundation.

Heart of the operation

Boyer’s lab employs students at the undergraduate, graduate, and postdoc levels from engineering, life sciences, and computer sciences –– each of whom, Boyer says, brings unique expertise and value to the team.

“It’s important for me to have a lab where everyone feels welcome, and that they feel that they can contribute to these fundamental discoveries,” Boyer says.

The Boyer Lab often works with scholars across disciplines at MIT. “It’s really great,” Auld says. “You can investigate a problem using multiple tools and perspectives.”

One project, in partnership with George Barbastathis, a professor in mechanical engineering, uses image-based machine learning to understand structural differences within cardiomyocytes when the proteins that signal cells to develop have been manipulated. Auld generates high-resolution images that the machine learning algorithms can analyze.

Another project, in collaboration with Ed Boyden, a professor in the Department of Biological Engineering as well as the McGovern Institute for Brain Research, involves the development of new technologies that allow high-throughput imaging of cardiac cells. The cross-pollination across departments and areas of expertise at MIT, Boyer says, often has her feeling like “a kid in a candy shop.”

“That our work could ultimately impact human health is very fulfilling for me, and the ability to use our scientific discoveries to improve medical outcomes is an important direction of my lab,” Boyer says. “Given the enormous talent at MIT and the excitement and willingness of everyone here to work together, we have an unprecedented opportunity to solve important problems that can make a difference in people’s lives.”

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Source: https://news.mit.edu/2021/queen-hearts-laurie-boyer-0616

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Bioengineer

USC Stem Cell scientists make big progress in building mini-kidneys

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The organoids, which resemble a kidney’s uretic buds, provide a way to study kidney disease that could lead to new treatments and regenerative approaches for patients

A team of scientists at the Keck School of Medicine of USC has created what could be a key building block for assembling a synthetic kidney. In a new study in Nature Communications, Zhongwei Li and his colleagues describe how they can generate rudimentary kidney structures, known as organoids, that resemble the collecting duct system that helps maintain the body’s fluid and pH balance by concentrating and transporting urine.

“Our progress in creating new types of kidney organoids provides powerful tools for not only understanding development and disease, but also finding new treatments and regenerative approaches for patients,” said Li, the study’s corresponding author and an assistant professor of medicine, and of stem cell biology and regenerative medicine.

Creating the building blocks

The first authors of the study, PhD student Zipeng Zeng and postdoc Biao Huang, and the team started with a population of what are known as ureteric bud progenitor cells, or UPCs, that play an important role in early kidney development. Using first mouse and then human UPCs, the scientists were able to develop cocktails of molecules that encourage the cells to form organoids resembling uretic buds–the branching tubes that eventually give rise to the collecting duct system. The scientists also succeeded in finding a different cocktail to induce human stem cells to develop into ureteric bud organoids.

An additional molecular cocktail pushed ureteric bud organoids–grown from either mouse UPCs or human stem cells–to reliably develop into even more mature and complex collecting duct organoids.

The human and mouse ureteric bud organoids can also be genetically engineered to harbor mutations that cause disease in patients, providing better models for understanding kidney problems, as well as for screening potential therapeutic drugs. As one example, the scientists knocked out a gene to create an organoid model of congenital anomalies of the kidney and urinary tract, known as CAKUT.

In addition to serving as models of disease, ureteric bud organoids could also prove to be an essential ingredient in the recipe for a synthetic kidney. To explore this possibility, the scientists combined mouse ureteric bud organoids with a second population of mouse cells: the progenitor cells that form nephrons, which are the filtering units of the kidney. After inserting the tip of a lab-grown ureteric bud into a clump of NPCs, the team observed the growth of an extensive network of branching tubes reminiscent of a collecting duct system, fused with rudimentary nephrons.

“Our engineered mouse kidney established a connection between nephron and collecting duct–an essential milestone towards building a functional organ in the future,” said Li.

###

About the Study

The project brought together scientists from the USC/UKRO Kidney Research Center, Li’s primary affiliation; the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC; the departments of Medicine, and Stem Cell Biology and Regenerative Medicine; and the divisions of Nephrology and Hypertension, and Maternal Fetal Medicine. Additional authors include Riana K. Parvez, Yidan Li, Jyunhao Chen, Ariel C. Vonk, Matthew E. Thornton, Tadrushi Patel, Elisabeth A. Rutledge, Albert D. Kim, Jingying Yu, Brendan H. Grubbs, Jill A. McMahon, Núria M. Pastor-Soler, Kenneth R. Hallows and Andrew P. McMahon.

Twenty percent of this work was supported by federal funding from the National Institute of Diabetes and Digestive and Kidney Diseases (grant DK054364 and F31 fellowship DK107216). The remainder of the support came from departmental startup funding, UKRO foundation support, a USC Stem Cell Challenge Award, and the California Institute for Regenerative Medicine (CIRM) Bridges Program.

About Keck School of Medicine

Founded in 1885, the Keck School of Medicine of USC is one of the nation’s leading medical institutions, known for innovative patient care, scientific discovery, education, and community service. Medical and graduate students work closely with world-renowned faculty and receive hands-on training in one of the nation’s most diverse communities. They participate in cutting-edge research as they develop into tomorrow’s health leaders. With more than 900 resident physicians across 50 specialty and subspecialty programs, the Keck School is the largest educator of physicians practicing in Southern California.

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Source: https://bioengineer.org/usc-stem-cell-scientists-make-big-progress-in-building-mini-kidneys/

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Bioengineer

New AI model helps understand virus spread from animals to humans

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A new model that applies artificial intelligence to carbohydrates improves the understanding of the infection process and could help predict which viruses are likely to spread from animals to humans. This is reported in a recent study led by researchers at the University of Gothenburg.

Carbohydrates participate in nearly all biological processes – yet they are still not well understood. Referred to as glycans, these carbohydrates are crucial to making our body work the way it is supposed to. However, with a frightening frequency, they are also involved when our body does not work as intended. Nearly all viruses use glycans as their first contact with our cells in the process of infection, including our current menace SARS-CoV-2, causing the COVID-19 pandemic.

A research group led by Daniel Bojar, assistant professor at the University of Gothenburg, has now developed an artificial intelligence-based model to analyze glycans with an unprecedented level of accuracy. The model improves the understanding of the infection process by making it possible to predict new virus-glycan interactions, for example between glycans and influenza viruses or rotaviruses: a common cause for viral infections in infants.

As a result, the model can also lead to a better understanding of zoonotic diseases, where viruses spread from animals to humans.

“With the emergence of SARS-CoV-2, we have seen the potentially devastating consequences of viruses jumping from animals to humans. Our model can now be used to predict which viruses are particularly close to “jumping over”. We can analyze this by seeing how many mutations would be necessary for the viruses to recognize human glycans, which increases the risk of human infection. Also, the model helps us predict which parts of the human body are likely targeted by a potentially zoonotic virus, such as the respiratory system or the gastrointestinal tract”, says Daniel Bojar, who is the main author of the study.

In addition, the research group hopes to leverage the improved understanding of the infection process to prevent viral infection. The aim is to use the model to develop glycan-based antivirals, medicines that suppress the ability of viruses to replicate.

“Predicting virus-glycan interactions means we can now search for glycans that bind viruses better than our own glycans do, and use these “decoy” glycans as antivirals to prevent viral infection. However, further advances in glycan manufacturing are necessary, as potential antiviral glycans might include diverse sequences that are currently difficult to produce”, Daniel Bojar says.

He hopes the model will constitute a step towards including glycans in approaches to prevent and combat future pandemics, as they are currently neglected in favor of molecules that are simpler to analyze, such as DNA.

“The work of many groups in recent years has really revolutionized glycobiology and I think we are finally at the cusp of using these complex biomolecules for medical purposes. Exciting times are ahead,” says Daniel Bojar.

###

Title: Using Graph Convolutional Neural Networks to Learn a Representation for Glycans

Publication link: https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00616-1

The researchers have developed graph neural networks for the analysis of glycans. This artificial intelligence technique views a glycan as a graph and learns sequence properties that can be used to predict glycan functions and interactions. The findings have been published in Cell Reports.

Contact:

Daniel Bojar, assistant professor at the Wallenberg Centre for Molecular and Translational Medicine and the Department of Chemistry and Molecular
Biology, University of Gothenburg.

Phone number: +46 (0)722-099822

Email address: [email protected]

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Source: https://bioengineer.org/new-ai-model-helps-understand-virus-spread-from-animals-to-humans/

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AI

Why It Took 20 Years to ‘Finish’ the Human Genome—and Why There’s Still More to Do

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The release of the draft human genome sequence in 2001 was a seismic moment in our understanding of the human genome, and paved the way for advances in our understanding of the genomic basis of human biology and disease.

But sections were left unsequenced, and some sequence information was incorrect. Now, two decades later, we have a much more complete version, published as a preprint (which is yet to undergo peer review) by an international consortium of researchers.

Technological limitations meant the original draft human genome sequence covered just the “euchromatic” portion of the genome—the 92% of our genome where most genes are found, and which is most active in making gene products such as RNA and proteins.

The newly updated sequence fills in most of the remaining gaps, providing the full 3.055 billion base pairs (“letters”) of our DNA code in its entirety. This data has been made publicly available, in the hope other researchers will use it to further their research.

Why Did It Take 20 Years?

Much of the newly sequenced material is the “heterochromatic” part of the genome, which is more “tightly packed” than the euchromatic genome and contains many highly repetitive sequences that are very challenging to read accurately.

These regions were once thought not to contain any important genetic information but they are now known to contain genes that are involved in fundamentally important processes such as the formation of organs during embryonic development. Among the 200 million newly sequenced base pairs are an estimated 115 genes predicted to be involved in producing proteins.

Two key factors made the completion of the human genome possible:

1. Choosing a very special cell type

The newly published genome sequence was created using human cells derived from a very rare type of tissue called a complete hydatidiform mole, which occurs when a fertilized egg loses all the genetic material contributed to it by the mother.

Most cells contain two copies of each chromosome, one from each parent and each parent’s chromosome contributing a different DNA sequence. A cell from a complete hydatidiform mole has two copies of the father’s chromosomes only, and the genetic sequence of each pair of chromosomes is identical. This makes the full genome sequence much easier to piece together.

2. Advances in sequencing technology

After decades of glacial progress, the Human Genome Project achieved its 2001 breakthrough by pioneering a method called “shotgun sequencing,” which involved breaking the genome into very small fragments of about 200 base pairs, cloning them inside bacteria, deciphering their sequences, and then piecing them back together like a giant jigsaw.

This was the main reason the original draft covered only the euchromatic regions of the genome—only these regions could be reliably sequenced using this method.

The latest sequence was deduced using two complementary new DNA-sequencing technologies. One was developed by PacBio, and allows longer DNA fragments to be sequenced with very high accuracy. The second, developed by Oxford Nanopore, produces ultra-long stretches of continuous DNA sequence. These new technologies allow the jigsaw pieces to be thousands or even millions of base pairs long, making them easier to assemble.

The new information has the potential to advance our understanding of human biology including how chromosomes function and maintain their structure. It is also going to improve our understanding of genetic conditions such as Down syndrome that have an underlying chromosomal abnormality.

Is the Genome Now Completely Sequenced?

Well, no. An obvious omission is the Y chromosome, because the complete hydatidiform mole cells used to compile this sequence contained two identical copies of the X chromosome. However, this work is underway and the researchers anticipate their method can also accurately sequence the Y chromosome, despite it having highly repetitive sequences.

Even though sequencing the (almost) complete genome of a human cell is an extremely impressive landmark, it is just one of several crucial steps towards fully understanding humans’ genetic diversity.

The next job will be to study the genomes of diverse populations (the complete hydatidiform mole cells were European). Once the new technology has matured sufficiently to be used routinely to sequence many different human genomes, from different populations, it will be better positioned to make a more significant impact on our understanding of human history, biology, and health.

Both care and technological development are needed to ensure this research is conducted with a full understanding of the diversity of the human genome to prevent exacerbation of health disparities by limiting discoveries to specific populations.The Conversation

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image Credit: Arek SochaPixabay 

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Source: https://singularityhub.com/2021/06/13/why-it-took-20-years-to-finish-the-human-genome-and-why-theres-still-more-to-do/

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