fbpx
Connect with us

The Conversation

AI plus gene editing promises to shift biotech into high gear

Published

on

theconversation.com – Marc Zimmer, Professor of Chemistry, Connecticut College – 2024-06-06 07:47:02
AI knowledge combined with gene-editing precision opens the way to dial-a-protein.
KTSFotos/Moment via Getty Images

Marc Zimmer, Connecticut College

During her chemistry Nobel Prize lecture in 2018, Frances Arnold said, “Today we can for all practical purposes read, write and edit any sequence of DNA, but we cannot compose it.” That isn't true anymore.

Since then, science and technology have progressed so much that artificial intelligence has learned to compose DNA, and with genetically modified bacteria, scientists are on their way to designing and making bespoke proteins.

The goal is that with AI's designing talents and gene editing's engineering abilities, scientists can modify bacteria to act as mini factories producing new proteins that can reduce greenhouse gases, digest plastics or act as species-specific pesticides.

As a chemistry professor and computational chemist who studies molecular science and environmental chemistry, I believe that advances in AI and gene editing make this a realistic possibility.

Advertisement

Gene sequencing – reading life's recipes

All living things contain genetic materials – DNA and RNA – that provide the hereditary information needed to replicate themselves and make proteins. Proteins constitute 75% of human dry weight. They make up muscles, enzymes, hormones, blood, hair and cartilage. Understanding proteins means understanding much of biology. The order of nucleotide bases in DNA, or RNA in some viruses, encodes this information, and genomic sequencing technologies identify the order of these bases.

The Human Genome Project was an international effort that sequenced the entire human genome from 1990 to 2003. Thanks to rapidly improving technologies, it took seven years to sequence the first 1% of the genome and another seven years for the remaining 99%. By 2003, scientists had the complete sequence of the 3 billion nucleotide base pairs coding for 20,000 to 25,000 genes in the human genome.

However, understanding the functions of most proteins and correcting their malfunctions remained a challenge.

AI learns proteins

Each protein's shape is critical to its function and is determined by the sequence of its amino acids, which is in turn determined by the gene's nucleotide sequence. Misfolded proteins have the wrong shape and can cause illnesses such as neurodegenerative diseases, cystic fibrosis and Type 2 diabetes. Understanding these diseases and developing treatments requires knowledge of protein shapes.

Before 2016, the only way to determine the shape of a protein was through X-ray crystallography, a laboratory technique that uses the diffraction of X-rays by single crystals to determine the precise arrangement of atoms and molecules in three dimensions in a molecule. At that time, the structure of about 200,000 proteins had been determined by crystallography, costing billions of dollars.

Advertisement

AlphaFold, a machine learning program, used these crystal structures as a training set to determine the shape of the proteins from their nucleotide sequences. And in less than a year, the program calculated the protein structures of all 214 million genes that have been sequenced and published. The protein structures AlphaFold determined have all been released in a freely available database.

To effectively address noninfectious diseases and design new drugs, scientists need more detailed knowledge of how proteins, especially enzymes, bind small molecules. Enzymes are protein catalysts that enable and regulate biochemical reactions.

AI system AlphaFold3 allows scientists to make intricately detailed models of life's molecular machinery.

AlphaFold3, released May 8, 2024, can predict protein shapes and the locations where small molecules can bind to these proteins. In rational drug design, drugs are designed to bind proteins involved in a pathway related to the disease being treated. The small molecule drugs bind to the protein binding site and modulate its activity, thereby influencing the disease path. By being able to predict protein binding sites, AlphaFold3 will enhance researchers' drug development capabilities.

AI + CRISPR = composing new proteins

Around 2015, the development of CRISPR technology revolutionized gene editing. CRISPR can be used to find a specific part of a gene, change or delete it, make the cell express more or less of its gene product, or even add an utterly foreign gene in its place.

In 2020, Jennifer Doudna and Emmanuelle Charpentier received the Nobel Prize in chemistry “for the development of a method (CRISPR) for genome editing.” With CRISPR, gene editing, which once took years and was species specific, costly and laborious, can now be done in days and for a fraction of the cost.

Advertisement

AI and genetic engineering are advancing rapidly. What was once complicated and expensive is now routine. Looking ahead, the dream is of bespoke proteins designed and produced by a combination of machine learning and CRISPR-modified bacteria. AI would design the proteins, and bacteria altered using CRISPR would produce the proteins. Enzymes produced this way could potentially breathe in carbon dioxide and methane while exhaling organic feedstocks, or break down plastics into substitutes for concrete.

I believe that these ambitions are not unrealistic, given that genetically modified organisms already account for 2% of the U.S. economy in agriculture and pharmaceuticals.

Two groups have made functioning enzymes from scratch that were designed by differing AI systems. David Baker's Institute for Protein Design at the University of Washington devised a new deep-learning-based protein design strategy it named “family-wide hallucination,” which they used to make a unique light-emitting enzyme. Meanwhile, biotech startup Profluent, has used an AI trained from the sum of all CRISPR-Cas knowledge to design new functioning genome editors.

If AI can learn to make new CRISPR systems as well as bioluminescent enzymes that work and have never been seen on Earth, there is hope that pairing CRISPR with AI can be used to design other new bespoke enzymes. Although the CRISPR-AI combination is still in its infancy, once it matures it is likely to be highly beneficial and could even help the world tackle climate change.

It's important to remember, however, that the more powerful a technology is, the greater the risks it poses. Also, humans have not been very successful at engineering nature due to the complexity and interconnectedness of natural systems, which often leads to unintended consequences.The Conversation

Marc Zimmer, Professor of Chemistry, Connecticut College

Advertisement

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

The Conversation

Diabetes and obesity can damage the liver to the point of failure – but few people know their risk of developing liver disease

Published

on

theconversation.com – Madona Azar, Associate Professor of Medicine, UMass Chan Medical School – 2024-07-22 07:21:55
Insulin resistance links MASLD to several other metabolic diseases.
Kateryna Kon/Science Photo Library via Getty Images

Madona Azar, UMass Chan Medical School

Liver disease is frighteningly common worldwide.

Metabolic dysfunction-associated steatotic liver disease, or MASLD, is an umbrella term describing conditions related to a buildup of fat in the liver. Formerly known as nonalcoholic fatty liver disease, this condition affects 1 in 4 people worldwide. Among those with type 2 diabetes, insulin resistance, obesity or all three, the prevalence of MASLD increases to 3 in 4 people.

As a diabetologist, the possibility of liver disease is on my mind every time I see a patient. Understanding your risk of developing this common yet underrecognized condition is essential to treating it.

What is MASLD?

MASLD is a complex disorder with both environmental and genetic contributions. In its early stages, liver cells accumulate fat in a process called steatosis. Major sources of this fat include adipose tissue as well as fatty acids the liver makes in response to insulin resistance and excess caloric intake. This fat accumulation can enlarge the liver and interfere with its normal functioning.

Advertisement

Over time, fatty acids activate enzymes, which can produce toxic byproducts capable of causing liver cell injury, inflammation and scarring. This condition is better known as MASH, or metabolic dysfunction-associated steatohepatitis. Progression to MASH is more common in the presence of other risk factors such as type 2 diabetes, insulin resistance and metabolic syndrome.

Left unaddressed, MASLD and MASH can progress to liver scarring, failure and, in some cases, cancer. They also increase risk of death from cardiovascular disease and liver-related complications.

In the U.S., MASH is the leading cause of liver transplants due to hepatic cancer among women and in those 65 and older. It is also on track to overtake hepatitis B and C as the main reason people develop liver cancer and thus need a liver transplant.

Liver disease and type 2 diabetes

Three out of four people with type 2 diabetes have MASLD. Linking liver disease, type 2 diabetes and obesity is the key role insulin resistance plays in their genesis.

Obesity is associated with increased fat deposits around the internal organs and higher levels of fatty acids delivered to the liver. Accumulation of fat in the liver increases its resistance to insulin.

Advertisement

Normally, insulin suppresses glucose production in the liver when blood sugar is high. When the liver becomes resistant to insulin, it produces more glucose despite elevated blood sugar levels, which in turn contributes to the development of type 2 diabetes.

A 2015 meta-analysis found that people with MASLD have a nearly twofold greater risk of developing type 2 diabetes than those without the disease. MASLD is also more likely to progress to MASH in the presence of type 2 diabetes.

MASLD disproportionately affects certain ethnic groups. For instance, 1 in 5 people of Hispanic descent in the U.S. have MASLD, with or without diabetes. This is thought to be related to genetic mutations that affect how the liver cells process fat. One particular mutation more common in Hispanic people promotes steatosis by interfering with the cells' ability to clear fat deposits.

Treating MASLD and MASH

The silver lining is that management of obesity and type 2 diabetes – such as through lifestyle changes – is very similar to management of MASLD. The most critical early interventions for type 2 diabetes can also help with MASLD, and this is not surprising given how closely interrelated these two conditions are.

The best way to reverse the early stages of MASLD is with weight loss through healthy eating habits and regular exercise. The aim is to shed at least 5% to 10% of initial body weight, maintain that weight loss through sustainable and realistic lifestyle choices, and avoid excess alcohol intake to limit additional liver injury.

Advertisement

New medications to treat diabetes, such as GLP-1 receptor agonists like Ozempic and Mounjaro, as well as SGLT2 inhibitors like Jardiance or Invokana, have also shown benefit in early stages of MASLD. These drugs promote weight loss, which in turn improves MASLD. In addition, studies have shown that Ozempic and Mounjaro could reverse MASH, even with inflammation and fibrosis.

Older medications used for diabetes, such as pioglitazone, typically can also help reduce the progression of MASH by reducing insulin resistance.

Liver disease progresses in stages of increasing damage.

In people with severe obesity or who have not had success with lifestyle changes and weight loss drugs, bariatric surgery is another highly effective option to treat MASLD, as it is associated with significant and sustained weight loss.

New drugs are also in the pipeline. The Food and Drug Administration recently approved a new medication called resmetirom to treat MASH with advanced liver scarring.

However, a cure for this chronic disease remains elusive. This is why it is essential to diagnose MASLD as early as possible and use proven measures that can be maintained long term. Treatments and lifestyle changes need to be deployed as early as possible, before inflammation and scarring have firmly set in. MASH gets trickier to treat in more advanced stages when liver damage becomes irreversible. For instance, while Ozempic may help treat early MASH, it doesn't benefit patients with more advanced stages of liver scarring.

Advertisement

Ignorance is not bliss

Very few people are aware of MASLD and its implications, including those living with it. While roughly over 35% of U.S. adults have MASLD, less than 5% are aware they have liver disease.

MASH can be difficult to diagnose because it either causes no symptoms or can be mistaken for other conditions. Patients may have the condition for years and not be aware that it is slowly and meticulously causing damage. In that sense, MASH is strikingly similar to type 2 diabetes or high cholesterol.

Child measuring blood sugar levels via finger prick on device held by a clinician
Recognizing MASLD is the first step to treating it.
supersizer/E+ via Getty Images

Young people are increasingly being diagnosed with early-onset MASLD. Indeed, MASLD with MASH is the most common pediatric liver condition, affecting nearly 8% of children and adolescents and over 34% of children with obesity in the U.S. These children and adolescents are at high risk of developing type 2 diabetes and have a significantly increased lifetime risk of cardiovascular disease and cancer.

Health care costs for people with type 2 diabetes and MASH are estimated to reach US$55 billion over the next 20 years, accounting for 65,000 liver transplants, 1.37 million cardiovascular-related deaths and 812,000 liver-related deaths.

These grim statistics need not be if MASH is tackled early and aggressively.

If you are one of the millions of Americans with prediabetes or diabetes and are also overweight, you most likely have some degree of MASLD or MASH. Being aware of MASLD and getting checked is the first step to addressing it.

Advertisement

Promptly determining the best way to treat your MASLD or MASH is the next step. An early referral to a liver specialist will help you halt the progression of this challenging and common condition and take advantage of the treatment breakthroughs researchers have made in the past few years.The Conversation

Madona Azar, Associate Professor of Medicine, UMass Chan Medical School

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

Read More

The post Diabetes and obesity can damage the liver to the point of failure – but few people know their risk of developing liver disease appeared first on theconversation.com

Advertisement
Continue Reading

The Conversation

How high school athletes can safely prepare for the start of practice, and the warning signs of heat illness

Published

on

theconversation.com – Samantha Scarneo-Miller, Assistance Professor of Athletic Training, West Virginia University – 2024-07-19 07:30:16
The first two weeks of practice are hardest as the body acclimatizes.
Derek Davis/Portland Portland Press Herald via Getty Images

Samantha Scarneo-Miller, West Virginia University

High school sports teams start practices soon in what has been an extremely hot summer in much of the country. Now, before they hit the field, is the time for athletes to start slowly and safely building up strength and stamina.

Studies have found that the greatest risk of heat illness occurs in the first two weeks of team practices, while players' bodies are still getting used to the physical exertion and the heat. Being physically ready to start increasingly intense team practices can help reduce the risk.

I am an athletic trainer who specializes in catastrophic injuries and heat illnesses. Here's what everyone needs to know to help keep athletes safe in the heat.

Why should athletes restart workouts slowly?

One of the biggest risk factors for developing dangerous exertional heat illnesses is your physical fitness level. That's because how fit you are affects your heart rate and breathing, and also your ability to regulate your body temperature.

Advertisement

If an athlete waits until the first day of practice to start exercising, their heart won't be able to pump blood and oxygen through the body as effectively, and the body won't be as adept at dissipating heat. As a person works out more, their body undergoes changes that improve their thermoregulation.

That's why it's important for athletes to gradually and safely ramp up their activity, ideally starting at least three weeks before team practices begin.

How high school athletes can safely prepare for the start of practice, and the warning signs of heat illness
Taking breaks – ideally in the shade – and staying hydrated can help athletes avoid heat illnesses.
Ian Spanier/ImageSource via Getty Images

There is no hard and fast rule for how much activity is right for preparing – it varies by the person and the sport.

It's important to remember not to push yourself too hard. Acclimatizing to working out in the heat takes time, so start slow and pay close attention to how your body responds.

How hot is too hot for working out outside?

Anything that is hotter than normal conditions can be risky, but it varies around the country. A hot day in Maine might be a cool day in Alabama.

If it's significantly hotter outside than you're used to, you're more likely to get a heat illness.

Advertisement

To stay safe, avoid exercising outside in the hottest periods. Work out in the shade, or in the early mornings or evenings when the sun's rays aren't as hot. Wear loose clothing and light colors to dissipate and reflect as much heat as you can.

Hydration is also important, both drinking water and replenishing electrolytes lost through sweating. If your urine is light-colored, you are likely hydrated. Darker urine is a sign of dehydration.

Football teammates, without pads or helmets, take a break around coolers of water on a hot August day.
Players need to stay hydrated and start practices slowly, without heavy equipment, to allow their bodies time to acclimate to the exertion and heat.
Shawn Patrick Ouellette/Portland Portland Press Herald via Getty Images

What does acclimatization look like for teams?

Once team practices start, many states require heat acclimatization processes that gradually phase in activity, though their rules vary. Some states require 14 days of heat acclimatization. Some require six days or none. Some only require it for football.

Athletes who get a head start on acclimatization can help their bodies adapt faster and more efficiently to the heat. Regardless of what your state requires, all athletes participating in all sports should acclimatize carefully.

Heat acclimatization involves adding more strain during the workout every few days, but taking care not to add too much.

Advertisement

For example, instead of starting the first day of practice with full pads and full contact in football, players might start with just the helmets for the first few days.

A line of linemen practice tackling while wearing helmets and pads.
Contact practices generate body heat, and full pads and helmets hold that heat in. More than 50 high school football players died from heat illnesses between 1996 and 2022.
AP Photo/Rogelio V. Solis

Acclimatization is also about limits: Holding practice only once a day in the beginning and capping how many hours players practice each day can help avoid putting too much strain on their bodies too fast. Coaches and athletic trainers must also keep an eye on the wet bulb global temperature – the combination of heat, humidity, radiation and wind speed – to gauge the heat risk to players and know when to limit or cancel practice.

This isn't just for football. Whether it's soccer, track and field, softball or baseball, heat illnesses do not discriminate. A Georgia basketball player died after collapsing during an outdoor workout in 2019 – she was accustomed to practicing indoors, not in the heat.

What are warning signs an athlete is overheating?

If a player starts to slow down or gets lethargic, that may be a sign that they're overheating. You might see evidence of central nervous system problems, such as confusion, irritability and being disoriented. You might see someone stumbling or trying to hold themselves up.

Most of the time, someone with exertional heatstroke will be sweating. They might have red skin and be sweating profusely. Sometimes a person with heat stress can lose consciousness, but most of the time they don't.

Illustration of an athlete shows symptoms of heat exhaustion and heat stroke
Signs of heat illness in athletes and what to do about it.
Alexander Davis for Arizona State University, Korey Stringer Institute

What should you do if someone appears to have a heat illness?

If someone appears to be suffering from heat illness, cool them down as fast as possible. Find a tub you can put the person in with water and ice. Keep their head out of the water, but cool them as fast as possible.

Immersion in a cool tub is best. If you can't find a tub, put them in a shower and put ice around them. Even a tarp can work – athletic trainers call it the taco method: Put the patient in the middle of the tarp, put some water in with ice, and hold up the sides to oscillate them slowly so you're moving the water from side to side.

Advertisement

Every sports team should have access to a cooling vessel. About half the states require it. As that expands, these safety practices will likely trickle down to youth sports, too.

If a player appears to be suffering from heatstroke, cool them down and call 911. Having a comprehensive emergency action plan ensures that all personnel know how to respond.

What else can teams do to prepare?

Exertional heatstroke is a top cause of sports-related death across all levels of sports, but proper recognition and care can save lives.

Athletic trainers are vital for sports programs because they are specifically trained to recognize and manage patients suffering from exertional heatstroke and other injuries. As hot days become more common, I believe all sports programs, including high school sports programs, should have an athletic trainer on staff to keep players safe.The Conversation

Samantha Scarneo-Miller, Assistance Professor of Athletic Training, West Virginia University

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

Advertisement

Read More

The post How high school athletes can safely prepare for the start of practice, and the warning signs of heat illness appeared first on theconversation.com

Continue Reading

The Conversation

Fewer bees and other pollinating insects lead to shrinking crops

Published

on

theconversation.com – Rachel Mallinger, Professor of Entomology, University of Florida – 2024-07-19 07:30:29
Insects are the primary pollinators of most flowers and crops.
Niklas_Weidner/500px via Getty Images

Rachel Mallinger, University of Florida

Many plants, from crops to carnations, cannot bear fruit or reproduce without bees, beetles, butterflies and other insects to pollinate them. But the population of insect pollinators is dropping in the U.S., due in part to pesticides, climate change, invasive plants and diminished habitats. Rachel Mallinger, assistant professor of entomology at the University of Florida, explains why these insects are in decline and how homeowners can create yards and gardens that are good for pollinators.

Rachel Mallinger discusses insect pollination.

has collaborated with SciLine to bring you highlights from the discussion that have been edited for brevity and clarity.

What kind of insects pollinate?

Rachel Mallinger: A lot of different insects pollinate. Insects visit flowers for many purposes, often for food, to get nectar or to get pollen. Sometimes they'll visit flowers to mate or to lay eggs or as refuge. Bees are the primary pollinators for a lot of plants, but flies, wasps, beetles and butterflies also play an important role.

Advertisement

How ecologically critical are insect pollinators?

Mallinger: A small percentage of flowering plants are pollinated primarily by wind, but new research suggests that as much as 90% require animal pollinators. Although birds, bats and other mammals also pollinate, insects are the main pollinators for the vast majority of those plants.

Without insects and their pollination, these plants would not be able to reproduce, and we would see a dramatic decline in plant diversity and abundance. Without insect pollinators, these plants wouldn't produce the seeds and the fruit that feed many animals – including people.

Have insect pollinator populations declined?

Mallinger: Recent studies have shown pretty dramatic declines in insects generally, and this has been shown even in conservation lands. So we think that in highly developed areas, insect declines are probably even more dramatic.

Advertisement

I study primarily native wild bees. Here in North America, we have between 4,000 and 5,000 species. For many species, we don't know if they're declining. Of the ones that we do have some information on, it's estimated that about half are declining and about a quarter are imperiled and potentially on the road to going extinct.

The insect pollinators that tend to be most at risk are ones that are specialists – those that require really unique, specialized food or nesting resources. Also ones that already have a limited range. For example, maybe they are found only on islands or in a small area.

Although many bee populations are in danger, there's much you can do to help.

What about the economic importance of insect pollinators?

Mallinger: Crops pollinated by animals, primarily insects, make up about one-third of our agricultural production in terms of acreage. A study in the state of Georgia found over US$360 million per year in crop pollination services provided by insects in that state alone.

What do insect pollinators need to be healthy?

Advertisement

Mallinger: Aside from pollen and nectar, some insect pollinators require additional food sources. For example, butterflies in the caterpillar stage need foliage from their host plants.

Other insect pollinators, like wasps and flies, are carnivores in the larval stage, so during that time they need to eat small arthropods – like spiders and centipedes – and insects.

Beyond that, they need nesting habitat. The majority of our insect pollinators nest below ground, and so they need ground that is relatively undisturbed, bare and accessible. Other pollinators nest in woody debris, stems and reeds. And some pollinators, like butterflies, just lay their eggs on host plants.

Additionally, pollinators need environments that are free from toxins. So they need environments that are not regularly sprayed with pesticides, including insecticides.

What stressors are leading to declines in insect pollinator populations?

Advertisement

Mallinger: I would say there are five main stressors.

Land use change is one. This can be the conversion of wild lands to agriculture or to development.

Climate change is another stressor. It changes the average temperature that these pollinators are experiencing and increases the chance of extreme temperatures and weather events. Hurricanes and flooding can be really detrimental and destroy the habitat for pollinators.

Third, pesticides and other chemicals in our environment that are toxic.

Invasive plants can be really detrimental for pollinators. They can take over an area and replace the native plants that pollinators depend on. That's four.

Advertisement

And finally, pathogens and parasites.

All five of these stressors can interact. For example, climate change may increase the likelihood of invasive plant species, pathogens and parasites thriving. Land use change can also increase the likelihood of invasive species.

What can homeowners do to help pollinators?

Mallinger: Planting a diversity of flowering plants for pollinators is one of the best things you can do. Aim to have at least three plants flowering at any given time, and look for a diversity of flower colors and shapes. Different pollinators have different preferences. You can have flowers that are yellow, blue, purple, pink, red and white.

In terms of floral shapes, plant some flowers that are flat and are accessible for pollinators with small mouthparts. And also plant some flowers with medium-length tubes, and some with long tubes.

Advertisement

Focus on native plants and try to seek out plants that might not just be the common types that you find in the big box stores. Go to native plant nurseries and seek out resources online.

Additionally, try to have nesting habitat in your garden. If the space allows, have some woody debris around for the pollinators that nest above ground. This can include things like logs, stems and reeds. Also manage your area to be as chemical-free as possible. This includes reducing pesticide use.

Keep in mind that many pollinators that nest below ground are not aggressive and are solitary. It's just one individual pollinator and her nest.

Watch the full interview to hear more.

SciLine is a free service based at the American Association for the Advancement of Science, a nonprofit that helps journalists include scientific evidence and experts in their stories.The Conversation

Rachel Mallinger, Professor of Entomology, University of Florida

Advertisement

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

Read More

The post Fewer bees and other pollinating insects lead to shrinking crops appeared first on theconversation.com

Continue Reading

News from the South

Trending