Connect with us

The Conversation

Customizing mRNA is easy, and that’s what makes it the next frontier for personalized medicine − a molecular biologist explains

Published

on

Customizing mRNA is easy, and that’s what makes it the next frontier for personalized medicine − a molecular biologist explains

One of the advantages of mRNA is its scalability.
DrAfter123/DigitalVision Vectors via Getty Images

Angie Hilliker, University of Richmond

While using mRNA as medicine is new, mRNA has been inside you for your entire life. The cells in your body create mRNAs that serve as instructions to make specific proteins you need to function. Researchers can create new mRNAs to correct those instructions when they aren’t working.

I am a molecular biologist who studies how cells control their mRNAs to make the proteins they need, a basic question of how life works at the cellular level. While most scientists studying mRNAs are not creating new drugs, this fundamental understanding of how mRNA works laid the foundation for other scientists to create effective mRNA medicines like COVID-19 vaccines.

By tweaking these instructions, scientists can create powerful new medicines to repair a variety of problems in your cells.

What does mRNA do?

To understand what the mRNAs in your cells are doing for you, let’s start with its more well-known relative, DNA.

DNA is like a set of cookbooks full of different recipes, or genes, to make proteins. People make about 100,000 different proteins that are essential for normal function, such as breaking down nutrients and carrying out other important chemical reactions.

When cells need to make one of those proteins, they don’t read the recipe directly from DNA. Instead, they make a copy in the form of a similar molecule – that’s the mRNA. The “m” stands for messenger, as mRNA contains the message, or recipe, that codes for a protein. About one-third of a cell’s energy is devoted to maintaining the proteins you need, so cells are well equipped to recognize, use and then destroy mRNA once it’s no longer needed.

Diagram illustrating flow of DNA transcription to RNA translation to protein
mRNA is the intermediary between DNA and protein.
Rujirat Boonyong/iStock via Getty Images

The language of mRNA is made of four building blocks called nucleotides, nicknamed A, U, C and G. The recipe to make a protein contains only three-letter words, meaning there are just 64 possible words. Scientists know exactly which words correspond to each protein building block, so they can easily read an mRNA recipe and know what protein will be made. Mutations in the DNA cookbook can alter or delete an mRNA recipe, leading to disease-causing mistakes in critical proteins.

Why do mRNAs make great medicine?

While mRNA has been within us all along, it took decades of research for scientists to understand how cells recognize mRNA and use it to make protein. But it eventually became clear that mRNA could be a powerful medical tool.

Since scientists understand how mRNAs code for proteins, they can easily create recipes for any protein. These recipes can be edited to meet the needs of the patient, whether this means providing a whole new mRNA recipe or tweaking an existing one to make a slight variation of the protein.

Producing mRNA treatments is also scalable because scientists can make large amounts of mRNA in the lab. The method to make one mRNA is the same for all mRNAs, unlike typical drugs where each compound has its own unique chemistry and requires different manufacturing methods. It’s like learning how to make risotto: Once you’ve learned the basic recipe, you can make endless variations.

Another benefit of using mRNAs as drugs are cells’ natural ability to destroy them when they aren’t needed. Since mRNAs aren’t permanent, doses can be easily changed to meet the changing needs of the patient.

mRNA vaccines beyond COVID-19

The COVID-19 vaccines from Moderna and Pfizer-BioNTech are the first mRNA-based medicines to gain FDA approval. When these vaccines are injected into your arm, the mRNA is absorbed into some of your cells, which read the mRNA recipe and make the spike protein the virus uses to invade cells. Your immune system recognizes this spike protein as foreign and makes antibodies that prepare your body to attack the virus if you encounter it later.

These mRNA vaccines demonstrate the flexibility of mRNA-based therapies. As the virus that causes COVID-19 mutates, new viral variants can evade existing antibodies and cause new waves of illness. However, scientists are able to sequence new mRNA recipes based on these variants and tweak the vaccine recipes to match them. Boosters containing these edited recipes teach your body to make new antibodies that target the latest versions of the viral spike protein.

YouTube video
The Pfizer-BioNTech and Moderna COVID-19 vaccines were the first to use mRNA for immunization.

There are already clinical trials underway for other mRNA-based vaccines, including vaccines for seasonal flu, herpes and respiratory syncytial virus.

There are also many more vaccines in earlier stages of development to combat diseases like norovirus, Lyme disease, Zika and shingles.

mRNA as treatment for disease

The potential for mRNA-based medicine extends beyond vaccines to prevent infectious disease. One example is the use of mRNA to treat cancer.

Some mRNA cancer treatments work like vaccines by training your immune system to specifically target cancer cells. As cancer cells grow, they rapidly gain mutations in many genes. Cancer vaccines contain mRNA recipes based on mutations commonly found in certain types of tumors. When injected into the body, the mRNAs from the vaccines allow normal cells to make those mutated proteins and broadcast them to the immune system, ramping up production of antibodies. These antibodies bind to cancer cells and mark them for immune attack.

Finding the correct protein target for a given cancer is essential. Ideally, the target is unique to the cancer cell so the immune system doesn’t attack healthy cells. The target protein should also be easy for the immune system to sense, making surface proteins good targets. Cancer vaccines, like BioNTech’s BNT-111 for melanoma, target the most common cancer mutations in hope of helping many patients. But patients won’t benefit from the treatment if their cancer cells don’t have those particular mutations.

Because it is so easy to change the mRNA recipes, cancer vaccines can be part of a personalized medicine plan where doctors sample a patient’s tumor, sequence key genes and adjust the mRNA treatment to include recipes specific to that patient’s cancer. Clinical trials using this personalized approach for pancreatic cancer are underway.

The future of mRNA-based medicine

Many diseases arise from cells making the wrong protein, a mutant version of protein or too little of the normal protein. If scientists can deliver a corrected version of the mRNA recipe to enough affected cells, then the mRNA will provide the means to make the proper protein.

Scientists are exploring the use of mRNA to treat heart disease, neurodegenerative disease, bone loss and much more. Although most of these studies are still very early in development, they provide hope for future treatments using mRNA for protein replacement therapies.

For example, one mRNA drug increases the formation of new blood vessels, which can improve wound healing in diabetic patients who have poor blood circulation and higher amputation risks. Another example is using mRNAs to treat propionic acidemia, a disease where children have low levels of two liver proteins that normally prevent toxic byproducts from building up in the body.

The ability to easily customize and produce mRNA increases their potential as effective, personalized therapies – with fewer side effects – that can help many people.The Conversation

Angie Hilliker, Associate Professor of Biology, University of Richmond

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

The Conversation

Out-of-balance bacteria is linked to multiple sclerosis − the ratio can predict severity of disease

Published

on

theconversation.com – Ashutosh Mangalam, Associate Professor of Pathology, University of Iowa – 2025-03-03 14:03:00

Out-of-balance bacteria is linked to multiple sclerosis − the ratio can predict severity of disease

The myelin sheaths insulating neurons are damaged in multiple sclerosis.
Steve Gschmeissner/Science Photo Library/Brand X Pictures via Getty Images

Ashutosh Mangalam, University of Iowa

Multiple sclerosis is a disease that results when the immune system mistakenly attacks the brain and spinal cord. It affects nearly one million people in the U.S. and over 2.8 million worldwide. While genetics play a role in the risk of developing multiple sclerosis, environmental factors such as diet, infectious disease and gut health are major contributors.

The environment plays a key role in determining who develops multiple sclerosis, and this is evident from twin studies. Among identical twins who share 100% of their genes, one twin has a roughly 25% chance of developing MS if the other twin has the disease. For fraternal twins who share 50% of their genes, this rate drops to around 2%.

Scientists have long suspected that gut bacteria may influence a person’s risk of developing multiple sclerosis. But studies so far have had inconsistent findings.

To address these inconsistencies, my colleagues and I used what researchers call a bedside-to-bench-to-bedside approach: starting with samples from patients with multiple sclerosis, conducting lab experiments on these samples, then confirming our findings in patients.

In our newly published research, we found that the ratio of two bacteria in the gut can predict multiple sclerosis severity in patients, highlighting the importance of the microbiome and gut health in this disease.

Microscopy image of large clump of rod-like bacteria
Akkermansia is commonly found in the human gut microbiome.
Zhang et al/Microbial Biotechnology, CC BY-SA

Bedside to bench

First, we analyzed the chemical and bacterial gut composition of patients with multiple sclerosis, confirming that they had gut inflammation and different types of gut bacteria compared with people without multiple sclerosis.

Specifically, we showed that a group of bacteria called Blautia was more common in multiple sclerosis patients, while Prevotella, a bacterial species consistently linked to a healthy gut, was found in lower amounts.

In a separate experiment in mice, we observed that the balance between two gut bacteria, Bifidobacterium and Akkermansia, was critical in distinguishing mice with or without multiple sclerosis-like disease. Mice with multiple sclerosis-like symptoms had increased levels of Akkermansia and decreased levels of Bifidobacterium in their stool or gut lining.

Bench to bedside

To explore this further, we treated mice with antibiotics to remove all their gut bacteria. Then, we gave either Blautia, which was higher in multiple sclerosis patients; Prevotella, which was more common in healthy patients; or a control bacteria, Phocaeicola, which is found in patients with and without multiple sclerosis. We found that mice with Blautia developed more gut inflammation and worse multiple sclerosis-like symptoms.

Even before symptoms appeared, these mice had low levels of Bifidobacterium and high levels of Akkermansia. This suggested that an imbalance between these two bacteria might not just be a sign of disease, but could actually predict how severe it will be.

We then examined whether this same imbalance appeared in people. We measured the ratio of Bifidobacterium adolescentis and Akkermansia muciniphila in samples from multiple sclerosis patients in Iowa and participants in a study spanning the U.S., Latin America and Europe.

Our findings were consistent: Patients with multiple sclerosis had a lower ratio of Bifidobacterium to Akkermansia. This imbalance was not only linked to having multiple sclerosis but also with worse disability, making it a stronger predictor of disease severity than any single type of bacteria alone.

Microscopy image of clusters of rod bacteria
Bifidobacterium both produces and consumes mucin, a glycoprotein that protects the gut lining.
Paola Mattarelli and Monica Modesto/Katz Lab via Flickr, CC BY-NC

How ‘good’ bacteria can become harmful

One of the most interesting findings from our study was that normally beneficial bacteria can turn harmful in multiple sclerosis. Akkermansia is usually considered a helpful bacterium, but it became problematic in patients with multiple sclerosis.

A previous study in mice showed a similar pattern: Mice with severe disease had a lower Bifidobacterium-to-Akkermansia ratio. In that study, mice fed a diet rich in phytoestrogens – chemicals structurally similar to human estrogen that need to be broken down by bacteria for beneficial health effects – developed milder disease than those on a diet without phytoestrogens. Previously we have shown that people with multiple sclerosis lack gut bacteria that can metabolize phytoestrogen.

Although the precise mechanisms behind the link between the Bifidobacterium-to- Akkermansia ratio and multiple sclerosis is unknown, researchers have a theory. Both types of bacteria consume mucin, a substance that protects the gut lining. However, Bifidobacterium both eats and produces mucin, while Akkermansia only consumes it. When Bifidobacterium levels drop, such as during inflammation, Akkermansia overconsumes mucin and weakens the gut lining. This process can trigger more inflammation and potentially contribute to the progression of multiple sclerosis.

Our finding that the Bifidobacterium-to-Akkermansia ratio may be a key marker for multiple sclerosis severity could help improve diagnosis and treatment. It also highlights how losing beneficial gut bacteria can allow other gut bacteria to become harmful, though it is unclear whether changing levels of certain microbes can affect multiple sclerosis.

While more research can help clarify the link between the gut microbiome and multiple sclerosis, these findings offer a promising new direction for understanding and treating this disease.The Conversation

Ashutosh Mangalam, Associate Professor of Pathology, University of Iowa

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

Read More

The post Out-of-balance bacteria is linked to multiple sclerosis − the ratio can predict severity of disease appeared first on theconversation.com

Continue Reading

The Conversation

How are clouds’ shapes made? A scientist explains the different cloud types and how they help forecast weather

Published

on

theconversation.com – Ross Lazear, Instructor in Atmospheric and Environmental Sciences, University at Albany, State University of New York – 2025-03-03 07:18:00

Lenticular clouds, like this one over a mountain in Chile, can look like flying saucers.
Bilderbuch/Design Pics Editorial/Universal Images Group via Getty Images

Ross Lazear, University at Albany, State University of New York

Curious Kids is a series for children of all ages. If you have a question you’d like an expert to answer, send it to curiouskidsus@theconversation.com.


How are clouds’ shapes made? – Amanda, age 5, Chile


I’m a meteorologist, and I’ve been fascinated by weather since I was 8 years old. I grew up in Minnesota, where the weather changes from wind-whipping blizzards in winter to severe thunderstorms – sometimes with tornadoes – in the summer. So, it’s not all that surprising that I’ve spent most of my life looking at clouds.

All clouds form as a result of saturation – that’s when the air contains so much water vapor that it begins producing liquid or ice.

Once you understand how certain clouds develop their shapes, you can learn to forecast the weather.

A view showing typical cloud heights shows tall cumulonimbus clouds, low level cumulus and high-level cirrus.
Cloud types show their general heights.
Australian Bureau of Meteorology

Cotton ball cumulus clouds

Clouds that look like cartoon cotton balls or cauliflower are made up of tiny liquid water droplets and are called cumulus clouds.

Often, these are fair-weather clouds that form when the Sun warms the ground and the warm air rises. You’ll often see them on humid summer days.

A horse or donkey next to river bank with puffy clouds in the sky.
Cumulus clouds over Lander, Wyo.
Ross Lazear, CC BY-ND

However, if the air is particularly warm and humid, and the atmosphere above is much colder, cumulus clouds can rapidly grow vertically into cumulonimbus. When the edges of these clouds look especially crisp, it’s a sign that heavy rain or snow may be imminent.

Wispy cirrus are ice clouds

When cumulonimbus clouds grow high enough into the atmosphere, the temperature becomes cold enough for ice clouds, or cirrus, to form.

Clouds made up entirely of ice are usually more transparent. In some cases, you can see the Sun or Moon through them.

Streaks of high white clouds look like paintbrush strokes
Cirrus clouds over the roof of Bard College in Annandale-on-Hudson, N.Y.
Ross Lazear, CC BY-ND

Cirrus clouds that forms atop a thunderstorm spread outward and can form anvil clouds. These clouds flatten on top as they reach the stratosphere, where the atmosphere begins to warm with height.

However, most cirrus clouds aren’t associated with storms at all. There are many ice clouds associated with tranquil weather that are simply regions of the atmosphere with more moisture but not precipitation.

Fog and stratus clouds

Clouds are a result of saturation, but saturated air can also exist at ground level. When this occurs, we call it fog.

In temperatures below freezing, fog can actually deposit ice onto objects at or near the ground, called rime ice.

YouTube video
Reading clouds, with the National Oceanic and Atmospheric Administration.

When clouds form thick layers, we add the word “stratus,” or “layer,” to the name. Stratus can occur just above the ground, or a bit higher up – we call it altostratus then. It can occur even higher and become cirrostratus, or a layer or ice clouds.

If there’s enough moisture and lift, stratus clouds can create rain or snow. These are nimbostratus.

How mountains can create their own clouds

There are a number of other unique and beautiful cloud types that can form as air rises over mountain slopes and other topography.

Lenticular clouds, for example, can look like flying saucers hovering just above, or near, mountaintops. Lenticular clouds can actually form far from mountains, as wind over a mountain range creates an effect like ripples in a pond.

A cloud appears to stream off the side of a tall mountain peak.
A banner cloud appears to stream out from the Matterhorn, in the Alps on the border between Italy and Switzerland.
Zacharie Grossen via Wikimedia, CC BY

Rarer are banner clouds, which form from horizontally spinning air on one side of a mountain.

Wind plays a big role

You might have looked up at the sky and noticed one layer of clouds moving in a different direction from another. Clouds move along with the wind, so what you’re seeing is the wind changing direction with height.

Cirrus clouds at the level of the jet stream – often about 6 miles (10 kilometers), above the ground – can sometimes move at over 200 miles per hour (320 kilometers per hour). But because they are so high up, it’s often hard to tell how fast they are moving.


Hello, curious kids! Do you have a question you’d like an expert to answer? Ask an adult to send your question to CuriousKidsUS@theconversation.com. Please tell us your name, age and the city where you live.

And since curiosity has no age limit – adults, let us know what you’re wondering, too. We won’t be able to answer every question, but we will do our best.The Conversation

Ross Lazear, Instructor in Atmospheric and Environmental Sciences, University at Albany, State University of New York

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

Read More

The post How are clouds’ shapes made? A scientist explains the different cloud types and how they help forecast weather appeared first on theconversation.com

Continue Reading

The Conversation

Who’s who at the Vatican?

Published

on

theconversation.com – Daniel Speed Thompson, Associate Professor of Religious Studies, University of Dayton – 2025-03-03 07:18:00

Who’s who at the Vatican?

Deacons take part in a mass in St. Peter’s Basilica that was supposed to be presided over by Pope Francis.
AP Photo/Alessandra Tarantino

Daniel Speed Thompson, University of Dayton

For more than two weeks, eyes have been on the Vatican, awaiting news about Pope Francis’ health. The pope has been at Rome’s Gemelli Hospital since Feb. 14, 2025, being treated for double pneumonia and other complications.

When a pope is ill, resigns or passes away, who steps in? And who else helps lead the Holy See? The Conversation U.S. asked Daniel Speed Thompson, a theologian at the University of Dayton, for some insight into Vatican City.

Who are the most powerful people at the Vatican, besides the pope?

The Vatican houses the central government of the Catholic Church and is also an independent city-state. The pope is both the head of the Catholic Church and head of state.

In order to govern both, he has the Roman Curia, meaning “court.” In modern terms, the Curia is the papal bureaucracy. It is an extension of the pope’s authority.

In Catholic doctrine, the pope has the highest authority in the church. He can exercise it alone or with the College of Bishops, made up of all the bishops in the world. Bishops named by the pope to the office of “cardinal” can, if under 80 years old, vote to elect a new pope. Some cardinals, but by no means all, serve in the papal Curia in Rome.

Besides the pope, curial officials who oversee important aspects of the church’s political and religious life are often powerful figures. For example, the secretariat of state, headed by Cardinal Pietro Parolin, oversees relations with other countries and international organizations. It also oversees the Vatican’s diplomatic corps.

Two men in black robes with red skullcaps and red sashes walk on a paved road, flanking a man in white robes.
Pope Francis smiles as he walks alongside Vatican Secretary of State Pietro Parolin, left, and Cardinal Giuseppe Versaldi at the Vatican in 2014.
AP Photo/Gregorio Borgia

The Dicastery – “department” – for the Doctrine of the Faith, led by Cardinal Víctor Manuel Fernández, addresses questions about correct Catholic teaching on faith and morals. The Dicastery of Bishops, headed by Cardinal Robert Prevost, coordinates the nominations of new bishops around the world.

All these officials work under the authority of the pope, advocating for and implementing his agenda. For example, Prevost has suggested that all Catholics should be involved in the selection of bishops. This idea is linked with Francis’ call for a more “synodal” church: one that is less hierarchical and shaped by lay Catholics’ concerns and challenges.

If a pope can’t fulfill his duties, who steps in?

When a pope dies – or resigns, like Benedict XVI did in 2013 – the governance of the Catholic Church formally falls to the College of Cardinals. However, the authority of the college is very limited. On their own, cardinals cannot make any significant decisions concerning faith, morals and worship. Nor can they undo previous papal decisions or change church laws about electing a new pope.

All the heads of the dicasteries lose their office upon the death or resignation of a pope. The College of Cardinals serves as a caretaker government whose primary purpose is to prepare for the election of the new pope and oversee day-to-day workings of the Vatican.

One cardinal, known as the “camerlengo,” is responsible for confirming the pope’s death or resignation. He then assumes control over the pope’s residence and coordinates the funeral, if needed. The camerlengo also takes custody of the Vatican’s property in Rome and supervises details for the upcoming conclave.

A man wearing a priest's collar gestures as he speaks, sitting in front of a framed portrait of Pope Francis.
Cardinal Camerlengo Kevin Farrell talks with The Associated Press in his office in Rome in 2018.
AP Photo/Paolo Santalucia

The day-to-day business of the Catholic Church continues, but no big decisions can be made in the absence of a pope. The church cannot appoint new bishops, and the Vatican cannot start new diplomatic efforts.

Are officials at the Vatican often nominated to be pope?

Sometimes. Francis was a cardinal from Argentina before his election as pope and had not served in the Roman Curia. However, Benedict XVI, Francis’ predecessor, did serve as the prefect of the Congregation – now called Dicastery – for the Doctrine of the Faith. Some recent popes served in the Curia earlier in their career but not immediately before their election.

What do you wish more people understood about the Vatican?

Three things. First, the Vatican is unlike any organization in the world. Its religious mission and political status rest on nearly 2,000 years of history. This complicated story provides a unique tradition that anchors the institution of the Catholic Church, but can also block the church from critical self-examination and renewal.

Second, the Vatican is like every organization in the world. Vatican officials can be faithful to the highest standards of their religion, truly wishing to serve the church and the common good of humanity. But they can also be flagrantly immoral, even criminals, and careerist seekers of status or luxury. Francis has consistently called out priests and bishops who see themselves as somehow superior by virtue of their office or their ordination.

Finally, compared with the massive bureaucracies of modern governments and corporations, the Vatican is relatively small and not as wealthy as it is often portrayed.

Although the Curia manages a vast international organization, its resources are far closer to my own midsize Catholic university than to the U.S. government or Apple. Vatican City and the Holy See employ about 2,000 people, with an operating budget of about US$835 million.

Yes, the Catholic Church has wealth – and the ongoing problem of deficits and financial corruption. But the Vatican’s resources pale in comparison with what a modern state or large company can muster.The Conversation

Daniel Speed Thompson, Associate Professor of Religious Studies, University of Dayton

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

Read More

The post Who’s who at the Vatican? appeared first on theconversation.com

Continue Reading

Trending