A small factor makes a big impact on genome editing – EurekAlert

image:

Although the specificity of CRISPR-based gene-editing is highly accurate and versatile, the efficiency of installing those edits has been low. In this paper, the Adamson lab describes a more efficient prime editor. Illustration by Caitlin Sedwick for Princeton University.

Credit: Caitlin Sedwick for Princeton University

By Caitlin Sedwick for the Princeton University Department of Molecular Biology

Through years of engineering gene-editing systems, researchers have developed a suite of tools that enable the modification of genomes in living cells, akin to genome surgery. These tools, including ones based on a natural system known as CRISPR/Cas9, offer enormous potential for addressing unmet clinical needs, underscored by the recent FDA approval of the first CRISPR/Cas9-based therapy. A relatively new approach called prime editing enables gene-editing with exceptional accuracy and high versatility, but has a critical tradeoff: variable and often low efficiency of edit installation. In other words, while prime edits can be made with high precision and few unwanted byproducts, the approach also often fails to make those edits at reasonable frequencies. In a paper that appeared in print in the journal Nature on April 18th, 2024, Princeton scientists Jun Yan and Britt Adamson, along with several colleagues, describe a more efficient prime editor.

Prime editing systems minimally consist of two components: a modified version of the protein element of CRISPR/Cas9 and a ribonucleic acid (RNA) molecule called a pegRNA. These components work together in several coordinated steps: First, the pegRNA binds the protein and guides the resulting complex to a desired location in the genome. There, the protein nicks the DNA and, using a template sequence encoded on the pegRNA, reverse transcribes an edit into the genome nearby. In this way, prime editors write exact sequences into targeted DNA.

"Prime editing is such an incredibly powerful genome editing tool because it gives us more control over exactly how genomic sequences are changed, Adamson said.

At the outset of their study, Adamson and Yan, a graduate student in Adamsons research group and the Department of Molecular Biology, reasoned that unknown cellular processes may aid or hinder prime editing. To identify such processes, Yan laid out a conceptually simple plan: First, he would engineer a cell line that would emit green fluorescence when certain prime edits were installed. Then, he would systematically block expression of proteins normally expressed within those cells and measure editing-induced fluorescence to determine which of those proteins impact prime editing. By executing this plan, the team identified 36 cellular determinants of prime editing, only one of whichthe small RNA-binding protein Lapromoted editing.

Although promoting prime editing is obviously not a normal function of the La protein, our experiments showed that it can strongly facilitate the process, Yan said.

Within cells, La is known to bind specific sequences often found at the ends of nascent small RNA molecules and it protects those RNAs from degradation. The Princeton team recognized right away that the pegRNAs deployed in Yans first experiments likely contained those exact sequences, called polyuridine tracts, as they are a typical but often overlooked byproduct of pegRNA expression in cells. Subsequent experiments suggested that such pegRNAs inadvertently harness Las end-binding activity for protection and to promote prime editing.

Motivated by their results, the team asked if fusing the part of La that binds polyuridine tracts to a standard prime editing protein could boost prime editing efficiencies. They were thrilled to find that the resulting protein, which they call PE7, substantially enhanced intended prime editing efficiencies across conditions and, when using some prime editing systems, left the frequencies of unwanted byproducts very low. Their results quickly drew the attention of colleagues interested in using prime editing in primary human cells, including Daniel Bauer at Boston Childrens Hospital and Harvard Medical School and Alexander Marson at the University of California, San Francisco. Together with scientists from these labs, the team of researchers went on to demonstrate that PE7 can also enhance prime editing efficiencies in therapeutically relevant cell types, offering expanded promise for future clinical applications.

"This work is a beautiful example of how deeply probing the inner workings of cells can lead to unexpected insights that may yield near-term biomedical impact, Bauer noted.

Citation: Jun Yan, Paul Oyler-Castrillo, Purnima Ravisankar, Carl C. Ward, Sbastien Levesque, Yangwode Jing, Danny Simpson, Anqi Zhao, Hui Li, Weihao Yan, Laine Goudy, Ralf Schmidt, Sabrina C. Solley, Luke A. Gilbert, Michelle M. Chan, Daniel E. Bauer, Alexander Marson, Lance R. Parsons & Britt Adamson.Improving prime editing with an endogenous small RNA-binding protein.Nature. 2024. DOI: https://doi.org/10.1038/s41586-024-07259-6

Funding for this work was provided by the National Institutes of Health (NIH) (R35GM138167, RM1HG009490, T32HG003284, DP2CA239597, UM1HG012660 [Princeton QCB training grant; NHGRI],and [T32GM007388 Princeton MOL training grant; NIGMS]); the Searle Scholars Program; thePrinceton Catalysis Initiative; CHDI Foundation; Princeton University; the Parker Institute for Cancer Immunotherapy (PICI); the Lloyd J. Old STAR award from the Cancer Research Institute (CRI); the Simons Foundation; the CRISPR Cures for Cancer Initiative; the Arc Institute; CRUK/NIH (OT2CA278665 and CGCATF-2021/100006); Pew-Stewart Scholars for Cancer Research award; the Doris Duke Foundation; the St Jude Childrens Research Hospital Collaborative Research Consortium; NHLBI (R01HL150669); the Fred Hutch Cooperative Center of Excellence in Hematology (U54 DK106829); the China Scholarship Council (CSC), based on the April 2015 Memorandum of Understanding between the CSC and Princeton University; the NCI (K00CA245718); and the Princeton University Flow Cytometry Resource Facility (NCI-CCSG P30CA072720-5921).

Experimental study

Improving prime editing with an endogenous small RNA-binding protein

3-Apr-2024

B.A. is an advisory board member with options for Arbor Biotechnologies and Tessera Therapeutics. B.A. holds equity in Celsius Therapeutics. L.A.G has filed patents on CRISPR tools and CRISPR functional genomics and is a co-founder of Chroma Medicine. A.M. is a co-founder of Arsenal Biosciences, Site Tx, Spotlight Therapeutics, and Survey Genomics, serves on the boards of directors at Site Tx, Spotlight Therapeutics and Survey Genomics, is a member of the scientific advisory boards of Arsenal Biosciences, Site Tx, Spotlight Therapeutics, Survey Genomics, NewLimit, Amgen, Tenaya, and Lightcast, owns stock in Arsenal Biosciences, Site Tx, Spotlight Therapeutics, NewLimit, Survey Genomics, PACT Pharma, Tenaya, and Lightcast, and has received fees from Arsenal Biosciences, Spotlight Therapeutics, Site Tx NewLimit, Survey Genomics, Gilead, 23andMe, PACT Pharma, Juno Therapeutics, Tenaya, Lightcast, Trizell, Vertex, Merck, Amgen, Genentech, AlphaSights, Rupert Case Management, Bernstein, GLG, ClearView Healthcare Partners, and ALDA. A.M. is an investor in and informal advisor to Offline Ventures and a client of EPIQ. The Marson Laboratory has received research support from Juno Therapeutics, Epinomics, Sanofi, GlaxoSmithKline, Gilead, and Anthem. C.C.W. and R.S. are co-founders of Site Tx. J.Y. and B.A. have filed a patent application on aspects of this work through Princeton University, and B.A. has previously filed other patents on CRISPR-based technologies. The remaining authors declare no competing interests.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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A small factor makes a big impact on genome editing - EurekAlert

Journalist Startled to Discover His Byline Has Been Replaced by Bot – Futurism

"The piece I had published more than ten years before was attributed to someone else." Vampire Independent

New journalistic nightmare unlocked: a defunct digital publication was revived from the media graveyard, only to have its Frankensteiners re-attribute old articles to bots.

Journalist andForever Warswriter Spencer Ackerman, a one-time employee of the since-sunsetted news site called the Washington Independent, this week recounted his shock to discover that his decade-old articles which had unfortunately been deleted alongside the rest of the website had mysteriously resurfaced. But while the words in the article were certainly Ackerman's, as the journalist explained in his newsletter, the byline attached to them was of one "Tyreece Bauer" an alleged "analyst and photographer in the field of technology" who does not appear to be real.

"On the zombie edition of the Washington IndependentI discovered, the piece I had published more than ten years before was attributed to someone else," reported Ackerman. "Someone unlikely to have ever existed, and whosebyline gracedan article it had absolutely never written."

Bauer is one of many fake "writers" now bylining re-attributed Washington Independentnews articles in the undead publication's archive. Meanwhile, also under fake bylines, the new andnot-so-improved Washington Independent is churning out new content: clickbait articles about topics like celebrities and crypto, bizarre affiliate mush, and hastily paraphrased copies of other outlets' reporting. And all of this, of course, strongly appears to be AI-generated.

Indeed, in the eroding, fragmented, and AI-laden 2024 media landscape, not even deleted bylines are safe from money-hungry SEO spammers and AI-generated nonsense.

What's more, as Ackerman points out, the Washington Independent doesn't appear to be the only vampiric site like this out there. In an X-formerly-Twitter thread, New York Times journalist Lydia DePillis reported that another website associated with the original Washington Independent's parent organization had also been revived, noting that it "looks legit at first but quickly degenerates into gibberish."

"It just strikes me as the saddest encapsulation of the trajectory of the media industry over the past 15 years," DePillis continued in the thread, "and everything is trash."

Ackerman and DePillis' findings are alarming for more reasons than one. From an individual writer's perspective, seeing your time and labor resurrected under a bot's byline is obviously terrible. And while SEO leeches buying and spinning up defunct websites for any remaining search engine credibility is anything but a new practice, doing so under the title of a once-legitimate news site is extra dangerous. Throw in the fake authors and the AI of it all, and you have a grotesque misinformation cocktail to potentially exploit.

One ray of hope? It's one of the many spammy practices that Google claims its new spam policies are going to crack down on.Still, consider this yet another grim postcard from the end of the internet as we know it.

More on AI and journalism: Wikipedia No Longer Considers CNET a "Generally Reliable" Source After AI Scandal

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Journalist Startled to Discover His Byline Has Been Replaced by Bot - Futurism

A week into 2024 and Big Tech has earned enough to pay off all 2023 fines – TechRadar

2023 surely was an eventful year in tech. To cite just a few key moments, generative AI became mainstream thanks to software like ChatGPT; we had to say goodbye to the iconic blue bird while welcoming Twitter's new name (I know very well the pain of writing 'X, formerly known as Twitter' over the past six months); and big tech companies got fined the most under GDPR's data abuses for a total of more than $3 billion.

Well, on the latter point, data protection regulators' efforts turned out to be not as effective as it was hoped they'd be.

Swiss privacy firm behind popular email and VPN service, Proton reported that only after a week into 2024 the likes of Meta, Google, Apple and Microsoft earned enough to pay off all last year's fines. Let's take a look at what needs to change and, most importantly, what you can do in the meantime to truly protect your privacy.

"Whats clear is that these fines, though they appear to be a huge amount of money, in reality are just a drop in the ocean when it comes to the revenues that the tech giants are making. In other words, they arent a deterrent at all," Jurgita Miseviciute, Head of Public Policy & Government Affairs at Proton, told me.

Researchers at Proton have calculated that Alphabet (Google's parent company) needs only a bit more than a day to pay off its $941 million fines. Amazon and Apple's earnings of just a few hours are then enough to repay their data protection's sanctions of $111.7 and $186.4 million respectively.

While biggest data abuse perpetrator Meta, which got a record $1.3bn fine for its (mis)handling of EU user data in May last year, managed to accumulate all the necessary money in just about five working days.

These findings make it clear that data regulators' fines, as founder and CEO of Proton Andy Yen put it, are "little more than pocket change for these companies" instead of a mean to stop them abusing users' data. Not only that, he said, as "these minuscule fines essentially give the green light to tech giants to run riot in a marketplace skewed in their favor."

It's also quite common that big tech firms might appeal to these sanctions or simply refuse to pay, delaying the repayment for years. Take how Google contested India's fine, for instance, about the Android-related inquiry for abusing its dominant position in the market which started in 2019.

On this point, Yen said: "Its the average consumer that's losing outfacing higher prices, less choice, and no privacy. It has to stop and we need real, tangible change that puts people first, not profits."

According to Miseviciute, there are two main things that must happen for things to really change.

Did you know?

Fully enforced in May 2023, the EU Digital Market Act (DMA) brought new obligations for tech companies to ensure fair competition and protect people's digital rights. A similar bill, so-called Digital Markets, Consumer and Competition Bill (DMCC) is currently passing through the UK Parliament, too.

For starters, she believes that governments have to issue fines with a real financial effect in order to fight back against big monopolies.

"Thats why fines up to even 20% of global revenues for breaches of laws such as the EUs DMA [Digital Market Act] and up to 10% in case of the proposed DMCC [Digital Markets, Competition and Consumers] Bill in the UK are a step in the right direction," she told me.

If heavier sanctions are important, they are not everything. Miseviciute explained that regulators need to combine these with practical measures such as enforced behavioral and structural changes, for example.

Again, she sees the EU quite well-placed to do so due to the new powers gained with the DMA. However, elsewhere there are also some small steps in this direction.

"We hope Googles antitrust trial in the US serves as a catalyst for comprehensive antitrust regulation on the other side of the Atlantic. We also see promising potential regulatory developments in South Korea, Japan, Australia and other major jurisdictions," she told me.

"If you open up the marketplace, and you give innovators like Proton a chance to succeed, youll get solutions that are more private and more secure for consumers."

As we have seen, 2023 was yet another hard year for our online privacy.

The US, for instance, still lacks a federal data protection law with the proposed ADPPA being stalled at the time of writing. Enforced in August last year, India's new privacy law was strongly criticized for favoring government and big tech instead of citizens. Well, where allegedly strong legislations are in place like in the EU, these seem to have not enough teeth just yet.

Commenting on this point, Miseviciute told me: "Until laws like the DMA in the EU and the proposed DMCC in the UK are effectively put into practice we are living in a world where big tech rules the internetand all our privacy is at the mercy of their surveillance capitalism business model."

Did you know?

Two thirds of people in the UK would rather lose their passport than access to their email account. Yet, despite these concerns, most of them lack the necessary knowledge and tools to protect their digital privacy. Big Tech knows that, researchers revealed.

The glimpse of light in this gloomy scenario is that it's ultimately our choice if we want to keep using data-hungry products. Luckily, there are some smaller companies offering privacy-first alternatives you can switch to.

On its part, Proton appear to have been working hard to cut Google out of our digital life. Likewise the popular service, the Swiss-based provider offers an encrypted email service Proton Mail (which even beat the big tech giant by landing with a standalone desktop app in December), secure calendar and its own cloud storage Proton Drive, too.

Proton's product offering also includes one of the best virtual private network apps on the market (Proton VPN) to help you boosting your anonymity while browsing among other things, as well as a password manager tool (Proton Pass) to secure all your login details. Even better as all the provider's services come both with free and paid plans.

However, Proton is just one of the many companies developing privacy-first alternatives to big tech software. Worth a mention there are also encrypted messaging app Signal if you wish to replace WhatsApp with a more secure application and Mullvad browser to make the switch from Safari and Chrome.

Compare today's best overall VPNs

We test and review VPN services in the context of legal recreational uses. For example: 1. Accessing a service from another country (subject to the terms and conditions of that service). 2. Protecting your online security and strengthening your online privacy when abroad. We do not support or condone the illegal or malicious use of VPN services. Consuming pirated content that is paid-for is neither endorsed nor approved by Future Publishing.

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A week into 2024 and Big Tech has earned enough to pay off all 2023 fines - TechRadar

Mayor Adams scores wins with Hochul policy rollouts, but more migrant aid still unclear – New York Daily News

Gov. Hochuls State of the State address on Tuesday and the policies she embedded in it include several new measures that are sure to be music to Mayor Adams ears but one noticeable omission was how to manage the migrant crisis in 2024.

Hochul floated plans to give local governments more power to combat unlicensed cannabis sellers and retail theft, and she aims to counter the harms of social media on teenagers through penalizing companies that rely on addictive algorithms all issues Adams has spoken about frequently.

Those measures are contained in a 180-page policy book Hochul put out as part of her State of the State address a book that also neglected to make mention of New York Citys migrant crisis, which had been included in last years policy book. Adams has struggled mightily to manage the migrant surge for nearly two years, and it ranks as one of his top priorities.

And while the words migrant and asylum seeker do not appear once in Hochuls policy book, the governor did raise the situation, however glancingly, during her Albany address, saying that she plans to focus more attention on the issue next week when she presents her budget plan.

Adams said he wasnt disappointed about the scant attention on migrants Tuesday, though.

We met a few weeks ago, and she clearly understands. We both agree this is a national problem, he told reporters in Albany after Hochuls speech. National government must deal with this issue, but its in our lap right now. We both understand that, and she did acknowledge that she will be talking about that in her budget.

Adams wouldnt say how much money in state aid hed like to see from Hochul for migrants in the upcoming budget, but said his budget honcho is working on it with the governors team.

Were going to work together to come to a real number to deal with the financial cost of this, Adams said.

Despite avoiding the migrant issue in large part on Tuesday, Hochul had other goodies to offer Adams.

The mayor has for weeks been calling for the ability to better enforce rules against unlicensed weed shops, which have proliferated in the city since the recreational use of cannabis was legalized in 2021 under a law that allows licensed shops to sell marijuana.

In the administrations policy book, Hochul vows to strengthen enforcement authority to expedite the closure of unlicensed businesses and deter this illicit activity through legislation that will beef up state and local governments ability to shut down unlicensed sellers.

Hochul also unveiled a plan to crack down on shoplifting, citing stats that show larcenies have risen 58% in the city since 2017. To do that, shell task a dedicated team of state police to build cases against organized theft rings and a new joint task force to coordinate efforts with local law enforcement district attorneys. In addition, Hochul plans to increase funding for state Crime Analysis Centers and direct money to cities that partner with them though it is not clear exactly how much money, if any, the city will receive as part of that initiative.

Social media companies which Adams has railed against for months will feel the heat from the state if Hochul has her way as well.

Shes floating a bill that would prohibit social media companies from using addictive feeds with kids under 18 unless a parent consents to them. Instead, it would allow for feeds that have a default chronology from users they already follow. Under her proposal, the state attorney general would be empowered to bring cases against companies with civil penalties of up to $5,000 per violation.

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Mayor Adams scores wins with Hochul policy rollouts, but more migrant aid still unclear - New York Daily News

JN.1 is Canadas new dominant COVID-19 subvariant. Heres what to know – Global News

A new COVID-19 subvariant, known as JN.1, has emerged and is now the prevailing strain across Canada, prompting health experts to caution that it may be more infectious and could even have extra symptoms.

Currently, the subvariant makes up the highest proportion of all COVID-19 variants, accounting for more than half (51. 9 per cent) of all infections in Canada, according to the latest data from the Public Health Agency of Canada (PHAC).

JN.1 was first detected in Canada on Oct. 9, and since then has rapidly increased.

If this virus continues to circulate at high levels, that means more virus, which means more mutations and more evolution, which means more of this same kind of issue happening repeatedly, warned Ryan Gregory, a professor of integrative biology at the University of Guelph, and evolutionary biologist.

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1:54 Low vaccine uptake fuels spike in respiratory illnesses: health officials

On Dec. 10, the JN.1 subvariant made up 26.6 per cent of all COVID-19 variants in Canada, but was not the dominant strain. At that time, HV.1 still made up 29 per cent of all subvariants, according to PHAC data. By Dec. 17, JN.1 made up the highest percentage (38.5 per cent) of all subvariants across Canada. Meanwhile, HV.1 fell to 24.4 per cent.

The World Health Organization (WHO) on Dec. 19 added JN.1 to its list of variants of interest, its second-highest level of monitoring. Despite the categorization, the health organization said JN.1 poses a low additional public health risk.

Two days later, on Dec. 21, PHAC labelled it as a variant of interest in Canada.

As the subvariant continues to circulate, here is what we know so far about JN.1.

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The JN.1 subvariant is a sublineage of BA.2.86 that emerged in Europe in late August 2023. It is another Omicron variant, according to PHAC. Gregory explained that JN.1 is a grandchild of BA.2.86. The original BA.2.86 probably evolved within a single person with a long-term infection over a year, he added.

So, somebody was infected. The virus continued to replicate and change within their body and then it reentered the rest of the population, he said. Once it gets back into the main population, its now evolving at the level of among hosts.

This in turn created the more competitive and successful JN.1. It featured a single alteration in the spike protein, enhancing its ability to effectively bind to cells, according to Gregory.

6:14 Holiday health update: Navigating the flu, RSV and COVID

It has massively managed to compete with the existing things that were out there, which suggests that its either very good at transmitting, and escapes immunity that is otherwise conferred by prior infection or previous vaccination, he said. So in other words, its different enough that your immune system, having been trained on older variants, doesnt recognize it as well.

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He also believes JN.1 may be the starting point for subsequent evolutions, much like the XBB variant. The XBB variant, another sublineage of Omicron, started circulating the world in late 2022. In 2023, some of its descendents, such as XBB.1.5 and EG.5, became dominating COVID-19 infections.

It is currently not known whether JN.1 infections produce different symptoms from other variants, health experts say.

The typical symptoms of COVID-19 according to the government are:

Additionally, Gerald Evans, an infectious disease specialist at Queens University in Kingston, Ont., said he has heard more people report gastrointestinal (GI) issues, such as diarrhea.

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The one thing I have been hearing about, they have GI symptoms, and these are not new, these have been recorded since COVID came out, he said. But anecdotally, the number of people having GI symptoms seems to be slightly higher, but you have to be careful with that because its an observational bias. But it does strike me that its becoming a bit more of a theme in the last month.

Gregory agreed with this observation but added that it may still be too early to tell if this is a hallmark symptom of the JN.1 variant.

He added that it is difficult to determine which symptoms go with what variant, especially when so many are circulating and there is less testing for COVID-19.

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Due to JN.1s fast growth, experts like Gregory say its either more transmissible or better at evading our immune systems. However, PHAC said in an email to Global News on Dec. 19, there is no evidence of increased severity associated with this variant.

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The WHO also stated last month that it is anticipated that this variant may cause an increase in COVID-19 cases amid a surge of infections of other viral and bacterial infections, especially in countries entering the winter season.

Since the spike protein is also the part that existing vaccines target, current vaccines should work against JN.1 and other lineages of BA.2.86, explained Evans. Preliminary evidence shows that protection by the XBB recombinant vaccine also guards against JN.1, he added. However, he cautioned, If it has been a year since your last vaccine or COVID infection, you may be more susceptible.

Personal protective measures are effective actions to help reduce the spread of COVID-19, PHAC stated. They include things like staying home when sick, properly wearing a well-fitted respirator or mask, improving indoor ventilation and practicing respiratory etiquette and hand hygiene.

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These measures are most effective when layered together, PHAC stated in an email.

Laboratory studies also suggest that the current therapeutic antiviral options, such as Paxlovid, available in Canada are expected to be effective against SARS-CoV-2 sub-lineages, PHAC added.

In some parts of the country, COVID-19 cases have been steadily increasing since the fall, yet the numbers appear to be stable now, according to Evans. However, while infection numbers remain stable, they are still very high and very steep, he warned, well beyond influenza, RSV and all the other viruses.

4:50 Kingston pharmacist urging residents to get vaccinated to avoid getting sick this winter season

He believes there may have been a holiday spike in COVID0-19 infections for several reasons, but most importantly noting that the uptake COVID-19 vaccine has been very poor.

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As of Dec. 8, PHAC reported that 14.6 per cent of eligible Canadians have received the updated vaccines targeting XBB.1.5.

The second reason, of course, is were in the middle of the respiratory virus season, Evans said. And although there are still a fair percentage of people who are being careful, there are a lot of people really have just gone back to what life was like before 2020. And. Thats, of course, a moment of opportunity for all these viruses to kind of take off.

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JN.1 is Canadas new dominant COVID-19 subvariant. Heres what to know - Global News

More Is Not Always Better: How The Las Vegas Swim Club Rebuilt To The National Stage – SwimSwam

This article originally appeared in the 2023 College Preview issue of SwimSwam Magazine. Subscribe here.

At the end of 2013, Peter Mavro and Amber Stewart were given the task of resurrecting a swim club on the verge of falling apart. With determination, a clear vision, and the influence of one of swimmings brightest minds in Russell Mark, they were able to make it happen.

When Mavro and Stewart first took over the Las Vegas Swim Club (LVSC) as head and assistant coach respectively, there were only 25 members and a 50% athlete retention rate. Numbers had been dropping for the club ever since their training facility, the Pavilion Center Pool, shut down in 2010 and they had to relocate. When Pavillion opened up in 2012 again, LVSC had their facility back, but the culture and outlook of the club was still very bleak.

At that time, LVSCs only purpose was to serve as a feeder organizationkids showed up to swim for three months, and then they either quit or moved on to the bigger, more lucrative Sandpipers of Nevada (SAND) club that was just ten minutes down the road. In other words, LVSCs biggest competition was the club that would later go on to produce six different Olympic and World Championship team members in the next decade.

There was just this constant revolving door of kids coming in and kids coming out, Mavro said. You cant build a consistent culture in that kind of scenario,

In front of them, Mavro and Stewart faced an organization that was barely holding itself together, and the fact that they were next-door neighbors with the biggest age group talent hotbed in the country only rubbed more salt into the wound. It was very easy for them to raise the white flag of surrender, but instead, they decided from day one that they were committed to reform.

I remember saying, what is our goal? What are we trying to be? Mavro said. From the day that I started working with this team, my mindset was to teach these kids, teach our families what it means to be in a committed environment, what it means to work hard, and not have it be a revolving door of swimmers.

It started from the little things, such as establishing attendance requirements, holding team meetings with parents, getting age groupers to have their cap and goggles on before practices started, never-ending practice early unless it was absolutely necessary, and finding alternate pools instead of canceling practice when the Pavillion wasnt available.

Another thing that Mavro and Stewart had to do was put their egos asideeven though Mavro is the head coach, he mainly works with age groupers, while assistant coach Stewart works with the older swimmers in the National Team group. Thats a non-traditional arrangement, with most clubs assigning their head coach to their fastest group of athletes.I believe in assessing my own strengths. That 10 to 14-year-old level is where my biggest strength is, so why wouldnt I be in that group? I believe Ambers biggest strength is to really inspire kids to do the impossible on a daily basis, so why wouldnt she be in that group? Mavro said. It just made so much sense to me, and thats why were set up the way were set up, so everybody can focus on their strengths.

Every small step that Mavro and Stewart took helped build LVSC from the bottom up, and in the end, it culminated into a growing culture of commitment and hard work.

Soon enough, the work of Mavro and Stewart began to pay off. In 2018, LVSC qualified swimmers for Sectionals for the first time. In 2019, Jack Gallob became LVSCs first Summer and Winter Juniors qualifier. In 2022, Owen Carlsen committed to Utah as the clubs first Power 5 Conference commitand his brother Max is on track to becoming one of the top recruits in the class of 2025. The number of swimmers in LVSC grew to around 200 and held steady, which is in line with Marvo and Stewarts mission to create a team that is both serious about swimming but still has that small, family-based feel.

Thats what separates us, Mavro said. When youre right next to another gigantic team thats shown a lot of success, you really have to give your families reason to believe that theyre getting something special. We want to build an environment where people want to bea hard work environment where the expectations are high, but we do not have coaches that yell, make kids feel bad about themselves, any of those kids. Its really about inspiring the kids to want to do it for themselves.

Were not just trying to throw a bunch of kids in the pool and let the best athletes find their way. We are trying to develop every single athlete to the best they can be.

More is not always better, better is better, Stewart added, making a statement that is frequently repeated throughout the national group that she coaches.

With LVSC and SAND being located so close together, they sometimes share a pool and hold practices back-to-back. When Stewart first began coaching LVSCs national group, she noticed that her swimmers acted complacently in front of the SAND swimmers, standing aside and waiting for them to finish warm-down even though it was LVSCs practice time. After time, though, Stewart decided that the dynamic and mentality of her program needed to change.

One of the first major things that I did as a coach was [make it clear that] we get in the pool at 4:30, we get in on time, Stewart said. There was a little bit of friction in the beginning, but [SAND] became very respectful of that and realized oh, okay, theyre serious. They arent gonna stand around just because we have this extra 300 to do.

Again, it was little things like these that sent out a message that LVSC was no longer going to be the pushover, and that they deserved the same respect as any other established club. Even though Stewart and Marvo dont want the entire identity of their club to revolve around being next to the Sandpipers, they acknowledge that getting over the hurdle of being overshadowed by their neighbors is a big part of what makes LVSC the club that they are today.

In the early days of Stewart and Mavros coaching, the LVSC had always looked towards SAND, with discussions at board meetings constantly being about trying to emulate what SAND does. Over time, however, they learned how to both co-exist with their neighborhood giant, as well as build their own, distinct, identity in their presence.

My mindset was, were not Sandpipers, were LVSC. We dont need to do what they do, and frankly, were not gonna be able to compete with them that way, Mavro said.If were trying to build a mini-Sandpipers, why would a swimmer or a family ever stay with us when the Sandpipers are already there?

Beyond the fact that they are both located in Las Vegas, LVSC and SAND dont actually have much in common. SAND has over 500 swimmers, while LVSC is less than half its size. LVSC has a lower volume training philosophy than SAND. SAND does three doubles a week, LVSC doesnt do doubles during the school year because of pool availability issueswhich Mavro thinks acclimatizes swimmers to the training hour limits in the NCAA. Not all swimmers need the same thing, and LVSC offered families in the Las Vegas area an alternate option if their swimmers dont fit the Sandpiper lifestyle.

We are very different programs, Stewart said. With the approach that we have, which is different from theirs, we have kept swimmers in our program that probably would not have stayed swimming otherwise.

Besides some tension here and there, not much bad blood exists between LVSC and SAND. Mavro is good friends with Sandpiper age group coach Chris Barberthe two of them are open books, talking about practice strategy, training, and season planning whenever they see each other.

At the end of the day, Mavro and Stewart believe that having SAND right next to them ultimately makes LVSC a stronger club, and they are grateful for the challenges that come with it.

Having the Sandpipers right next to us holds us to an incredibly high standard, Mavro said. We cannot get away with making lazy choices. As much as it can be frustrating, it is our greatest motivator by far. Were better because were right next to them.

The teams [of Las Vegas] have quality staff that are working against each other, but they are also working to build a really fast swimming community.

Yeah, theres friction and frustration, but at the end of the day, were all here to support each other and make the world of swimming together. Stewart added.

Less than ten years after their rebuild, LVSC was seeing the kind of national-level success that some much older clubs havent experienced before. Prior to 2019, the club didnt know what coaching Junior National and DI-caliber swimmers was likethey ran headlong into a lot of firsts and learned by doing.

When Jack Gallob, LVSCs first Winter Juniors qualifier, came to the National Team group for the first time, he was instantaneously moved from the slowest lane to the fastest lane with no in-betweens. It became clear that he was a one-of-a-kind type of swimmer, and shortly thereafter, Stewart began giving him sets that nobody else in the club was capable of doing.

Initially, the transition for Gallob was challenging. In fact, he even complained to Stewart that his situation wasnt fair. But Stewart didnt buy it.

I told [him], I think what youre trying to do is say that the definition of fair is that everybody gets the same thing. Stewart said. But if thats the definition of fair that I abide by as a coach, then Im not doing a good job, because my definition of fair is that everybody gets what they need. And [he needed] something that [was] different from the rest of the athletes in the pool.

And he remembers that conversationit was really impactful, and a light bulb switched. I think he realized, oh, okay, I dont wanna get away with less. I wanna get away with what I can do and maximize what I can do.

Three years after swimming at his first winter juniors in 2019, Gallob is now set to swim at Indiana University-Purdue (IUPUI) starting in the fall of 2023. Since 2019, he has taken his 100 back personal best from 50.21 to 49.18 and his 200 back personal best from 1:50.15 to 1:47.56, amongst drops in other events.

After Gallob, the success train just kept on rolling at LVSC, with Owen Carlsen excelling in distance freestyle and committing to Utah, and Max Carlsen becoming the 8th-fastest 15-year-old of all-time in the 1000 free. Joe Christ came into LVSC with a 2:27 200 free and dropped down to a 1:39 by the time he was a senior and committed to Air Force. At the Carlsbad Sectionals in March 2023, LVSC won first place in the small team division.

Once Gallob reached heights that had never been attained before, it caused a domino effect.

Seeing [Gallob] do it makes that belief for the next group of kids, Mavro said. When you see your teammates do these sorts of things, it does help you with that belief so that when the coach sits down with you and looks at your individual goals, lets say its making futuresAmber [can say] well, I think your goals need to be a little more higher than that. Youve got more in you, youve seen your teammates do it.

Stewart said that she and Mavro discuss goals with all of their swimmers, trying to make them ambitious and realistic. After deciding upon what their goals are, those goals will then get laminated and put in the gear bags of swimmers so they can be reminded of them every day.

Increasing success also means greater chances of a swimmer competing at the highest level in college, which was also a hurdle that Mavro and Stewart had to overcome, as they had never experienced intense college recruiting until recently. However, just like with everything else, they adapted.

Stewart, who swam in college herself at Brigham Young University, used her own NCAA connections to help her swimmers in the recruiting process. Gallob had relatives who swam for Kentucky, and they came over to LVSC to speak about the college experience. Ben Loorz, the head coach of the University of Las Vegas-Nevada held a PowerPoint night at the Pavillion once. In addition, Stewart herself listened to swimming podcasts and exchanged ideas with other coaches on Facebook to familiarize herself more with recruiting.

Its not my forte by any means, but having relationships and being willing to reach out to coaches when coaches reach out to us and making sure that were responsive to them is [something that Im trying to be better at], Stewart said. Were kind of learning as we go.

However, arguably the best resource for LVSC has been Russell Mark, who is best known for being USA Swimmings former High Performance Manager, and who now works for the American Swimming Coaches Association (ASCA). Mavro knew Mark from their time together at the University of Virginia, and the two are close friends. Frequently, Mark analyzes the strokes and techniques of LVSC swimmers via videos that Mavro sends him, and provides LVSC with connections to the great swimming community.

For example, LVSCs national group got invited to an ASCA clinic via Mark, where they got to meet names like Ohio State head coach Bill Dorenkott, Virginia head coach Todd DeSorbo, as well as Mel Marshall, the coach of world record holder Adam Peaty. At that clinic, DeSorbo arranged a time with Mavro and Stewart where they would be able to travel to Virginia and come watch one of their practices.

Its random for a small team in Las Vegas to happen to have access to what I would consider the greatest swimming mind in this country, Mavro said. Without Russell, we would not be where we are. Everything Ive done in coaching and developing the kids is based on everything Ive learned from him, as far as stroke technique.

In the end, however, everything circles back to the values that Mavro and Stewart had wanted to ingrain in LVSC from the very beginning. Its not about the accolades, college commits, or timesits about developing a family-friendly culture, and for swimmers to grow into the best versions of themselves inside and outside the pool.

I cant say how proud I am of what weve been able to do with our program and what our programs athletes dobecause if they dont buy in then Im out of a job, Mavro said. You cant have a national group if you dont instill the tools that the kids need to be there in the first place. I want to see the kids succeed, but I want to see the kids fail and learn from it and learn how to take that next step.

One of the things we hear oftentimesis your kids are always so nice and respectful. And that thats always going to be mean more than me than your kids were so fast.

Read more:

More Is Not Always Better: How The Las Vegas Swim Club Rebuilt To The National Stage - SwimSwam