1 month ago

Bioscience discoveries show the power of collaboration

Two recent research accomplishments in which the UAH Department of Biological Sciences closely collaborated with partners from outside the university illustrate the strength in such partnerships.

Dr. Jerome Baudry (pronounced Bō-dre), a molecular biophysicist and the Mrs. Pei-Ling Chan Chair in Biological Sciences, joined with Hewlett Packard Enterprises (HPE) to employ its Cray Sentinel supercomputer to rapidly identify 125 naturally occurring compounds that show promise as treatments for the COVID-19 coronavirus.

In separate research, Dr. Eric Mendenhall, a UAH associate professor of biological science, teamed with the HudsonAlpha Institute for Biotechnology to identify the function of 208 proteins responsible for orchestrating the regulation genes in the human genome. The research was published in Nature in July.

The partnerships were essential to the discoveries, says Dr. Paul Wolf, Biological Sciences chair, and UAH provides an ideal environment to nurture partnerships with industry and other entities.

“Solving complex problems requires integration of a diversity of thought,” Dr. Wolf says.

The Department of Biological sciences at UAH encourages faculty and students to work with each other and with local and national entities on collaborative projects, he says.

“The research successes of Eric Mendenhall and Jerome Baudry illustrate the kind of breakthroughs that can be made with such partnerships,” Dr. Wolf says. “We very much hope to see these collaborations grow in the future.”

Potential COVID treatments

Together Dr. Baudry’s lab and HPE used the Sentinel supercomputer to rapidly assess a batch of 50,000 chemicals to identify 125 naturally occurring compounds with a computational potential for efficacy against COVID-19.

The research was noted in a keynote speech by Antonio Neri, HPE president and CEO, at the HPE Discover Virtual Experience event. Neri told over 100,000 registrants from the computing, scientific and business worlds that the HPE collaboration with Dr. Baudry “allowed his research team to deliver results in weeks versus months or years.”

The idea for an alliance with HPE developed months before the COVID-19 crisis, following a meeting to discuss how to integrate natural products, artificial intelligence and supercomputing.

“One of the presenters, Dr. Rangan Sukumar, is a distinguished technologist in high-performance computing (HPC) and artificial intelligence at HPE,” says Dr. Baudry. “He talked to his colleagues there and they reached out to us to inquire about the possibility of working together.”

As the collaboration was becoming more operational the COVID-19 pandemic developed. Located in UAH’s Shelby Center for Science and Technology, the Baudry Lab was searching for potential precursors to drugs that would help combat the global pandemic.

“At HPE we are committed to being a force for good, and since the start of the COVID-19 outbreak, we have been on a mission to extend our technologies and resources to scientists on the front line of drug discovery,” says Bill Mannel, vice president and general manager of HPC at HPE.

“We found a perfect match with Dr. Baudry and his team at UAH, who have used our cloud-based supercomputer running in Microsoft Azure and a dedicated technical staff to support their research,” Mannel says.

By using the supercomputer through the cloud, the team was able to increase outcomes of drug candidates through biodiversity at an unprecedented speed, he says, saving them years of research and millions of dollars in costs.

“It has also been an honor helping Dr. Baudry realize his vision and be a part of the overall journey to advance treatment efforts to combat COVID-19 and end human suffering.”

The partnership marked the first time a supercomputer was used to assess the treatment efficacy of naturally occurring compounds against the proteins made by COVID-19.

“We used supercomputers to predict natural products most likely to bind to three proteins of the SARS-CoV-2 virus,” says Dr. Baudry. SARS-CoV-2 is the scientific name of the COVID-19 virus.

“Out of the 50,000 natural products that we looked at using supercomputers, we found several hundred to be predicted to be potentially binding on the proteins of interest,” he says. “We further found 125 – but there may be more – that are particularly interesting because they bind right where we want to, they are not too big, not too small and they have the chemical profiles of pharmaceuticals.”

There are many diverse natural sources for the chemicals of interest, Dr. Baudry says.

“Many are from relatively common medicinal plants that can be found in the U.S., and many are from more distant plants from Southeast Asia and South America, as well as from some ground and oceanic bacteria strains and fungi.”

A Biological Safety Level 3 laboratory in Memphis is testing natural products that were identified by the Baudry Lab for their activity against the COVID-19 virus. Chemical molecules found most efficacious will form the basis for future testing for efficacy, tolerance and adverse effects in human trials, a process that might include chemical modifications to make the drug more efficient, better tolerated or both.

“Every drug that ends up surviving this long and winding road of development and testing starts as a hit that binds to a protein. It is this initial event that we are modeling here using supercomputers,” Dr. Baudry says.

The fight against COVID-19 has created a new meeting of modern high-capacity artificial intelligence with humankind’s most ancient healing knowledge, Dr. Baudry says.

“Normally it would take a very long time and a lot of money to achieve that, but with the supercomputers we can perform this initial hit discovery step much faster and cheaper,” he says. “Even five years ago, this would not have been possible.”

Located in a Microsoft Azure data center in Texas, Sentinel made the work more rapid than ever before possible and an HPE team helped facilitate it. Dr. Baudry’s UAH team accessed Sentinel through the cloud with Microsoft Azure.

Sentinel is capable of computing 147 trillion floating point operations per second and can store 830,000 gigabytes of data. That’s as fast as the Earth’s entire population doing 20,000 calculations every second.

At the same time, Dr. Baudry’s lab also collaborated in other COVID-19 research with the Alabama Supercomputing Network and Oak Ridge National Laboratory in Tennessee.

Understanding how cells work

A close collaboration between the UAH lab of Dr. Mendenhall and the lab of Dr. Richard Myers, who is the president, M. A. Loya Chair in Genomics, science director and a faculty investigator at HudsonAlpha, resulted in new understanding of the function of 208 proteins responsible for orchestrating the regulation of genes in the human genome. These proteins and others play major roles in determining the type and function of new cells, a process known as differentiation.

The working partnership was a fundamental building block for the resulting discoveries, says Dr. Myers.

“We have greatly enjoyed and benefited from this close collaboration with Dr. Mendenhall and his team, which involves a combination of complex ‘wet-lab’ experiments and computational analysis and interpretation of large amounts of data,” Dr. Myers says.

“One of the most satisfying things about this work is that we are creating a knowledge base of how human genes are regulated that is being used by thousands of researchers and clinicians around the world,” he says. “The data and findings are made freely available rapidly to everyone, and this has helped to greatly speed up our understanding of the human genome.”

It is critical that genes be turned on and off in different cell and tissue types, but scientists haven’t had a good idea of how that was controlled, says Dr. Mendenhall.

“Ours and many other groups have been working for years to find what regions of the human genome controlled this turning on and off – what we call enhancers and promoters,” he says.

“We wanted to determine what proteins control this turning on and off. These are called transcription factors, and our group looked at where 208 of them function. It was a large number and we helped to add a significant amount of information to how genes are turned on and off.”

Transcription factors can make a cell into a heart cell, a liver cell or even a cancer cell. Their location along the DNA strand, or genome, is critical to what role a cell will play during its lifetime. The genome in each of our cells is identical. It’s the transcription factors that act as the switches to turn on or off genetic functions and differentiate the capabilities of one cell from another.

“We have close to 20,000 genes in our genome, and about 1,800 of these belong to the class called transcription factors, which is a pretty large portion of our genes,” says Dr. Mendenhall.

“These genes code for proteins that work in our nucleus to turn genes on or off by binding to the DNA. Once they bind to the DNA, which is tightly controlled by many chemical and biological mechanisms we don’t yet fully understand, they find a nearby target gene to usually turn on, but occasionally turn off.”

It’s important to have a complete catalog to get a full picture of how genes are controlled, Dr. Mendenhall says. That’s a key part of how humans develop from embryos and it’s important to how our cells do their jobs and keep us healthy.

“An incomplete picture leaves we scientists unsure whether we are missing key transcription factors, or of how to explain why certain transcription factors bind here but not there, or turn this gene on but not that one,” Dr. Mendenhall says. “We have a lot of outstanding questions and a lot of these questions will be easier to answer once we study all 1,800 transcription factors.”

Teams led by Dr. Myers and Dr. Mendenhall employed the latest rapid genetic sequencing techniques, running dozens of parallel experiments at one time to quickly locate and flag transcription factors in a lab-grown line of liver cancer cells called HepG2 that are used for research purposes.

The new discoveries came as part of the $31.5 million National Institutes of Health (NIH) Encyclopedia of DNA Elements (ENCODE) Project to further the construction of a comprehensive list of functional elements in the human genome. A scientific offspring of the Human Genome Project, the ENCODE Project launched in 2003 and is a scientific consortium that is tasked with creating and sharing genomics resources that are used by many scientists to study human health and disease.

Advances in a new technology called CRISPR-Cas9 hastened progress by allowing scientists to test almost any transcription factor. Key to the research was a procedure developed in 2015 by Dr. Myers and Dr. Mendenhall called CETCh-seq.

With CETCh-seq, scientists first use the CRISPR/Cas9 genetic editing technique to design a reagent to modify a genome in cells. Once they are flagged, in the second part of the CETCh-seq method a protocol called ChIP-seq tells them where the transcription proteins are located.

“It took a lot of dead ends,” Dr. Mendenhall says, “but we also found a lot of new questions to pursue that we couldn’t have predicted.”

(Courtesy of UAH)

4 hours ago

Alabama basketball completes the sweep against Auburn

Fresh off of winning the SEC regular season championship for the first time in 19 years, the Alabama Crimson Tide on Tuesday completed a sweep of Auburn for the first time in six years after defeating the Tigers at home 70-58.

Jayden Shackelford led the way for Alabama in Tuscaloosa, as the talented sophomore guard went 5-9 from behind the arc to finish with 23 total points in the win over Auburn.

Sophomore Jahvon Quinerly scored 11 points off of the bench and provided sparks for Alabama in crucial moments of the game.

While Alabama led by as much as 16 points in the first half, Auburn was able to cut the lead to five in the second. However, Alabama’s defense began to stiffen up, and seniors Herbert Jones and John Petty stalled the Tiger’s offense out before they could get too hot.

201

For the Tide, the three-ball has become a major part of their offense. Second-year head coach Nate Oats always tells his players to get at least one touch in the paint first before shooting. This green-light mentality is becoming more and more popular throughout college hoops.

Bama has done really well with this philosophy by becoming one of the most dominant teams from downtown in the conference. Tuesday’s game showed that even when the three doesn’t come through for the Tide, they have other ways of scoring.

Alabama drove the basketball extremely well in the second half against Auburn and proved to be the more physical team in their win on Tuesday night. When tournament time begins, they may have to lean on this more physical style of play in certain games.

The Tide have one more regular season game against Georgia in Athens on Saturday. Bama will look to finish the regular season on a win before the SEC Tournament in Nashville gets underway.

The Tide are currently projected to be a two seed in the upcoming NCAA Tournament.

Hayden Crigler is a contributing college football and college basketball writer for Yellowhammer News. You can contact him through email: hayden@yellowhammernews.com or on Twitter: @hayden_crigler.

4 hours ago

Alabama House recap: Bills to increase executive branch oversight, update sex ed language pass chamber

MONTGOMERY – The Alabama House of Representatives met Tuesday and passed six pieces of legislation, including bills that would increase oversight of executive branch agencies and update language in the state’s policy on sex education.

After convening shortly after 1:00 p.m. the chamber spent much of the next five hours in extended debate on two bills, with members of the Democratic Party engaging in protracted discussions of legislation they began their remarks saying they would ultimately vote for.

Seeing the most debate were HB 392 from Rep. Mike Jones (R-Andalusia) and HB 103 from Rep. Jamie Kiel (R-Russellville).

Jones’ bill creates a joint legislative committee to oversee large financial agreements made by the executive branch, and Kiel’s would prevent the state government from picking which businesses close during states of emergency.

456

More information on Kiel’s bill is available here.

The legislation from Jones, chair of the powerful Rules Committee, would create the Joint Legislative Oversight Committee on Obligation Transparency. The committee would have the authority to approve or disapprove of contracts, leases and agreements by the executive branch and the agencies therein.

Under the proposed law the committee would meet to review any financial agreement greater than $10 million or 5% of the agency’s annual appropriation from the State General Fund.

Making up the committee would be the chair, vice-chair and ranking minority members of the committees in each legislative chamber that oversee taxation.

The proposed oversight committee would be able to meet when the legislature is in or out of session. It would have to issue approval or disapproval within 45 days of a state agency submitting a proposed contract.

If the proposed committee disapproved of a contract it would be delayed from going into effect until the end of the current or next occurring general session of the legislature.

Jones noted in remarks on the floor that this delay would give lawmakers time to address via legislation the proposal disapproved of by the committee, and added that new legislation would be required to put a halt to any state contract of which the proposed committee disapproved.

HB 392 ultimately received unanimous support in the House, with a final vote of 98-0.

Also passing the House on Tuesday was HB 385 sponsored by Rep. Laura Hall (D-Huntsville). The bill updates language in the legal code that governs how Alabama educators must teach sex ed.

It also deletes from the Code of Alabama language that requires those teaching sex ed to emphasize that “homosexuality is not a lifestyle acceptable to the general public and that homosexual conduct is a criminal offense under the laws of the state.”

Rep. Terri Collins (R-Decatur) and Rep. Charlotte Meadows (R-Montgomery), two staunch conservatives with backgrounds in education policy, spoke in favor of the legislation on the House floor and voted for its passage. The bill passed the House on a vote of 69-30.

Three other pieces of lower profile legislation passed the chamber on Tuesday:

HB 255 from Rep. Randall Shedd (R-Cullman) that would add a tenth member to the advisory board of directors of the Department of Senior Services, and let ex officio members name a designee to serve in their place.

HB 330 from Rep. Alan Baker (R-Brewton) that would change the outdated language in the state legal code concerning video depositions in criminal prosecutions.

HB 136 from Rep. Chip Brown (R-Hollinger’s Island) that would designate the aquarium at Dauphin Island Sea Lab as the Official Aquarium of Alabama.

Henry Thornton is a staff writer for Yellowhammer News. You can contact him by email: henry@yellowhammernews.com or on Twitter @HenryThornton95.

8 hours ago

Alabama House passes bill that would block the government from picking and choosing which establishments close during states of emergency

MONTGOMERY – The Alabama House of Representatives passed a bill on Tuesday that would prevent the state government from designating which types of businesses were allowed to stay open in situations such as the one experienced during the advent of the coronavirus pandemic in the spring of 2020.

Sponsored by Rep. Jamie Kiel (R-Russellville), HB103 would not infringe on the governor or state health officer’s ability to implement public health guidance. It would only say that any business or house of worship that followed public health guidelines would be allowed to open.

“I think if it is safe enough to go to the liquor store and wear a mask and socially distance, then it is safe enough to go to church and wear a mask and socially distance,” argued Kiehl on the House floor.

285

The vote on the floor was 75 in favor and 22 opposed with three members abstaining.

The bill applies to declared states of emergency that involve a “pandemic, epidemic, bioterrorism event, or the appearance of a novel or previously controlled or eradicated infectious disease or biological toxin,” per the text of the legislation.

In explaining what inspired him to author the legislation, Kieh said of last spring, “I saw businesses in my town that were suffering,” adding that some small business owners he knew were “scared to death they were going to lose their livelihoods.”

Governor Ivey’s “Stay At Home” order, in place for most of April 2020, allowed major retailers like Walmart to remain open while smaller retail stores that did not sell groceries were forced to close.

Kiehl feels that this arrangement was unfair, and that small shops and establishments deserved the chance to stay open if able to implement the health guidelines. Ivey has expressed regret in recent months about creating the distinction between “essential” and “non-essential” businesses.

“[W]hat we were really doing is were we driving all the customers that would have been in all these other stores — in the small mom-and-pops, the Hibbetts of the world — we were driving all those to one central location to buy clothing. That cannot be good for the spread of the pandemic — to bring everybody together in one location or a few locations,” Kiel told FM Talk 106.5’s “The Jeff Poor Show.”

The National Federation of Independent Businesses (NFIB) is strongly supporting the passage of the legislation.

Kiel’s bill now heads to the Senate for further consideration.

Henry Thornton is a staff writer for Yellowhammer News. You can contact him by email: henry@yellowhammernews.com or on Twitter @HenryThornton95.

9 hours ago

Alabama Senate passes Vulnerable Child Compassion and Protection Act

MONTGOMERY — On a party line vote, the Alabama Senate on Tuesday passed SB 10, the Vulnerable Child Compassion and Protection Act.

Sponsored by Sen. Shay Shelnutt (R-Trussville), the bill would ban the performance of medical procedures and the prescription of puberty-blocking medications and sex-change hormones used as transgender therapies for minors, with certain exceptions.

The vote was 23-4, with the only four Democrats present all dissenting: Sens. Billy Beasley (D-Clayton), Vivian Figures (D-Mobile), Bobby Singleton (D-Greensboro) and Rodger Smitherman (D-Birmingham).

Shelnutt, since first introducing a version of the legislation last year, has said his goal in bringing the bill was to simply protect children from making harmful longterm decisions that they may later regret once more mature.

215

“The primary concern here is the health and well-being of Alabama’s children,” stated Shelnutt. “We must protect vulnerable minors who do not have the mental capacity to make life-altering decisions of this caliber. The efficacy and effects of these particular surgeries and methods of treatment are not well-sustained by medical evidence, and actions of this severity cannot be undone.”

“I believe it is our responsibility as lawmakers to do all we can to keep our children out of harm’s way,” he added. “Protecting minors from these powerful drugs and consequential procedures will help ensure they do not feel responsible to make a decision they may wish to later undo, ultimately causing more harm.”

The House Judiciary Committee last week approved as amended the lower chamber’s companion version of the bill, which is sponsored by Rep. Wes Allen (R-Troy). HB 1 now awaits consideration on the House floor.

In response to the passage of SB 10, Scott McCoy — SPLC interim deputy director for LGBTQ Rights & Special Litigation — released a statement.

“The Alabama State Senate is dangerously close to passing yet another piece of discriminatory legislation that likely will lead to long and expensive litigation at high cost to Alabama taxpayers,” McCoy decried.

Sean Ross is the editor of Yellowhammer News. You can follow him on Twitter @sean_yhn

10 hours ago

Alabama GOP Senate candidate Lynda Blanchard: 2020 election ‘stolen from President Trump’

Republican U.S. Senate candidate Lynda Blanchard on Tuesday called upon the Alabama House Constitution, Campaigns, and Elections Committee to vote down a bill that would legalize no-excuse absentee voting in the state, among other alterations of Alabama’s elections laws.

The committee is set to meet on Wednesday regarding HB 396, which is sponsored by State Rep. Laura Hall (D-Huntsville). The bill was originally backed by Secretary of State John Merrill, although he has now withdrawn his support for the measure.

Blanchard served in the administration of President Donald J. Trump as his ambassador to Slovenia, the home country of then-First Lady Melania Trump.

The Montgomery resident is Alabama’s only declared U.S. Senate candidate ahead of the 2022 race to replace retiring U.S. Senator Richard Shelby (R-AL). Blanchard in a written statement said HB 396 significantly weakens Alabama’s absentee balloting rules.

159

“Absentee balloting invites corruption, cheating, and fraud, so it should be allowed only in rare and unavoidable cases,” she said. “The bill that has been introduced in the Legislature leaves the door wide open for ballot harvesting and other abuses that allowed the recent presidential election to be stolen from President Trump.”

“The bill also begins a dangerous process of watering down Alabama’s election laws, which could lead to the repeal of our photo voter ID requirements and other safeguards that Republicans have put in place,” Blanchard continued.

She concluded, “Alabama should focus on strengthening, not weakening, our honest election reforms, and we certainly shouldn’t implement no-excuse absentee voting, which is often used by liberal Democrats who have refined election fraud and ballot stuffing into an art form.”

Lt. Governor Will Ainsworth (R-AL) and Congressman Mo Brooks (AL-05) have already voiced opposition to HB 396.

Sean Ross is the editor of Yellowhammer News. You can follow him on Twitter @sean_yhn