Category Archives: Biochemistry

Biochemistry

UA Researchers Develop Way to Test Water for Metal Pollutants – The University of Alabama

Research involving The University of Alabama created an easier way to detect harmful levels of heavy metals in water, which could help improve human health by boosting detection efforts by regulatory agencies, water utilities and commercial fishing.

Dr. Marco Bonizzoni

The new analytical method for detecting harmful levels of heavy metals such as cadmium, mercury and lead was created by combining chemical array sensing methods developed at UA with polymer synthesis capabilities at the University of Southern Mississippi, according to findings recently published in Advanced Functional Materials.

The work is part of a larger, multiyear collaboration led by the University of Mississippi and supported by the National Science Foundation to develop advanced polymer-based, selective sensing technologies for detecting and analyzing pollutants in the coastal aquatic ecosystems of the Gulf of Mexico, which host important fisheries, aquaculture, trading ports, and off-shore oil exploration and production industries.

The new method proved to be unusually robust and sensitive even in complex and challenging samples, down to the extremely low concentrations relevant for environmental monitoring applications in fresh- and saltwater, said Dr. Marco Bonizzoni, UA associate professor of chemistry and biochemistry.

Our method for these analyses uses less complex instrumentation, yet achieves sensitivity similar to established lab-based standard techniques, Bonizzoni said. Additionally, our system is simpler and more rugged than existing techniques, potentially opening the path towards development of a portable device for and point-of-sampling measurements.

At low levels, heavy metals are ubiquitous in the environment and some are essential nutrients for the ecosystem. At increased levels, mostly from human intervention, they threaten human, animal and ecosystem health. Exposure to heavy metals has been linked to neurological disease, organ failure and cancer.

Methods for their rapid and simple detection are a scientific and technological priority. Water utilities regularly monitor these potential contaminants in municipal water. Government regulatory agencies track heavy metals in waters as a proxy for potential contamination of marine life such as fish sold for consumption.

Bonizzoni, associate professor of chemistry and biochemistry, and his group created a simple method for detecting harmful levels of heavy metals in water.

Current methods require lugging water samples taken on location back to a lab for analysis, which is time consuming and requires additional measures to ensure the sample isnt contaminated. The new method could simplify this process greatly by allowing for direct on-site measurements.

For now, researchers demonstrated they can simplify analysis by testing samples taken from the site of the Deep Water Horizon oil spill in the Gulf, gathered by a group led by Dr. Alan Shillerfrom Southern Mississippi. The site near the destroyed oil rig and subsequent massive oil spill into the ocean in 2010 released heavy metals into the environment.

Former UA graduate student Dr. Michael Ihde, now a faculty member at Williams College, led the Bonizzoni groups efforts to combine their method for using an array of receptors in a chemical sensor with the polymer synthesis capabilities from a group led by Dr. Jason Azoulay at Southern Mississippi and his graduate student Joshua Tropp.

Researchers prepared bright fluorene-based light-emitting charged polymers with appended metal binding groups, and studied their interactions with metal pollutants, developing methods for their ultrasensitive detection and discrimination.

Through the collaboration, we made new polymers, we combined them in a physical sensing system, and we measured complex and challenging samples with it, Bonizzoni said.

After demonstrating this proof of principle, the research team will focus on streamlining the procedure to fit inside a portable sensing system that could be operated by most anyone as a self-contained testing device deployed on a boat or, possibly, on a buoy that passively and continuously monitors the water; however, that future is several steps away.

Contact

Adam Jones, UA communications, 205-348-4328, adam.jones@ua.edu

The University of Alabama, part of The University of Alabama System, is the states flagship university. UA shapes a better world through its teaching, research and service. With a global reputation for excellence, UA provides an inclusive, forward-thinking environment and nearly 200 degree programs on a beautiful, student-centered campus. A leader in cutting-edge research, UA advances discovery, creative inquiry and knowledge through more than 30 research centers. As the states largest higher education institution, UA drives economic growth in Alabama and beyond.

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UA Researchers Develop Way to Test Water for Metal Pollutants - The University of Alabama

Biochemistry

UAPB Alumnus Recommends a UAPB Education in Aquaculture/Fisheries for Research, Job Opportunities – UAPB News

Will Hehemann|School of Agriculture, Fisheries and Human Sciences

Andrew Maina, originally from the east African country of Kenya, says his lifelong interest in science led him to enroll in the University of Arkansas at Pine Bluffs (UAPB) graduate program in aquaculture/fisheries.

My father was a pharmacist, and I also started to get interested in science in elementary school, he said. In high school, I became really interested in biology. My love for the outdoors and wildlife started in Kenya but continues to play a part in my life in my new home of North Carolina. I frequently go hiking and birdwatching.

During his undergraduate studies at the University of Eastern Africa in Baraton, Kenya, Maina took a course on marine biology. This experience made him curious about studying a discipline of science largely new to him.

I became interested in further studying fish because they have unique physiologies compared to other groups of animals, he said. I visited with Dr. Rebecca Lochmann, chair of the UAPB Department of Aquaculture and Fisheries. Our conversation about her research on catfish piqued my interest. I had previously taken a graduate course in chemical separations and biochemistry at the University of Florida, which gave me the theoretical background in the type of tools and techniques used in her lab for research.

In 2012, he enrolled in the graduate program and started conducting research on channel catfish nutrition under the mentorship of Dr. Lochmann.

In the lab, I was able to build an entirely new skill set as we used biochemistry techniques and separation chemistry to investigate the nutritional composition of fish muscle and whole fish, Maina said. Dr. Lochmann was influential in providing guidance throughout my graduate studies and also in giving me opportunities to attend large conferences and present my original research.

After graduating from UAPB in 2016, Maina was employed by Smithers, a company that provides independent testing services for a range of industries and products.

I was hired as a study director for channel catfish nutrient equivalency studies with various genetically modified organisms (GMO) grain varieties meant for export to the Asian market, he said. We were testing catfish feeds formulated to incorporate GMO grains. Our job was to ensure GMO grains used in these feeds were similar enough to non-GMO strains. We also made sure the feeds did not have any negative effects on catfish growth.

Maina currently works for Catalent, Inc., a global pharmaceutical company, where he is responsible for performing drug substance and drug product stability analysis.

Before they hit the market, medicines must be tested to make sure whatever components listed on the label are actually in the tablet in those precise measurements, he said. Our work helps ensure that any drug released to the market is in full compliance with U.S. Food and Drug Administration standards.

Maina said he recommends an education at the UAPB Department of Aquaculture and Fisheries for students looking to gain quality research experience. In addition to the labs on campus, he said students can also pursue collaborative opportunities with organizations such as the Harry K. Dupree Stuttgart National Aquaculture Research Center in Stuttgart, Arkansas.

The research skills I gained at UAPB continue to help me in my career, he said. During my studies, I enjoyed working with professors and students from different backgrounds on research that truly supported Arkansas and the region.

The University of Arkansas at Pine Bluff offers all its Extension and Research programs and services without regard to race, color, sex, gender identity, sexual orientation, national origin, religion, age, disability, marital or veteran status, genetic information, or any other legally protected status, and is an Affirmative Action/Equal Opportunity Employer.

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Biochemistry

28-year-old Becomes First Black Woman to Earn PhD in Biochemistry at Florida International University – YEN.COM.GH – Yen.com.gh

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Student-athlete, Chantrell Frazier, has made history as the first Black woman to earn a doctoral degree in Biochemistry at Florida International University.

Frazier, 28, began her college journey at Historically Black College or University (HBCU), where she earned her bachelor's degree to give her the proper foundation to prepare her for graduate school.

It was also the same reason that inspired her to attend Savannah State University (SSU), according to Atlanta Black Star.

After making history, Frazier looks forward to continuing her studies at a postdoctoral teaching fellowship at Framingham State University in Massachusetts.

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The trailblazer plans to become a chemistry professor and champion the next generation of STEM leaders.

Still on education, YEN.com.gh previously reported that Lerato Jaca triumphed adversity to achieve her goals, becoming the first person in her family to bag a degree in 2020.

She understood what it meant for a Black girl to glean such a feat, more so, make history.

In a post on Twitter, Jaca disclosed that she graduated from the University of Cape Town, UCT, making history as her family's first graduate and doctor.

Meanwhile, YEN.com.gh earlier reported that Ray Curtis Petty Jr, ESQ is the definition of a fighter who overcame cycles of obstacles life threw at him to achieve his goal as a legal brain, becoming the first lawyer in his family.

Undaunted by the mountain of difficulties and childhood inadequacies, he triumphed and made history as his family's first-generation attorney.

Recounting his story on his Instagram account, he recalls being told by his teachers that he should be in special education classes. His coaches also doubted his ability to remember a playbook as a child, he said.

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Biochemistry

Designing the next generation of nanoscale electronics | Rowan Today | Rowan University – Rowan Today

Amid an ongoing semiconductor shortage delaying the production of cars, phones, computers, and televisions, a new research collaboration between Rowan University and Butler University seeks to develop computational tools for designing the next generation of nanoscale electronics. The $222,559 grant was awarded by the National Science Foundation.

It is becoming increasingly more difficult to create these computer chips.

The classical computing architectures are starting to reach their development potential, said principal investigator Erik Hoy, Ph.D., an assistant professor of chemistry and biochemistry in the College of Science & Mathematics. What we're looking to contribute to is the next generation of computer architectures.

These next-generation devices are incredibly small, but have enormous potential. Hoy and his research team will partner with a team from Butler University to develop new techniques to study these devices on a molecular level more effectively. Previous methods have limitations in their treatment of molecular electronic interactions, and a more comprehensive methodology is needed to ensure that nanoscale architectures deliver their promised performance gains.

Hoys software will treat electronic interactions in these devices to a degree that has not been done before. The software will help determine if nanoelectronics-based computer chips will function as engineers hoped. This tool will then be made publicly available for any researcher to use.

In the long run, it's intended to address a key supply chain problem, Hoy said. Were going to provide new tools, so that when people go to build these devices, they can predict their properties accurately so they know the device will behave as expected.

The grant will support Rowans materials science and engineering program by heavily involving both graduate and undergraduate students throughout the research.

One of my key goals is to help build the next generation of materials science and nanoscience-focused students in the U.S., Hoy said.

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Designing the next generation of nanoscale electronics | Rowan Today | Rowan University - Rowan Today

Biochemistry

Plant-based testosterone in pine pollen could be a goldmine for forestry – New Zealand Herald

Pine pollen is the fine yellow powder released by pine trees every spring that forms part of the reproductive life cycle of the tree. Photo / Supplied

Pine pollen containing a rare natural source of plant-based testosterone could prove a goldmine for New Zealand's forestry sector.

Pine Pollen New Zealand Limited, trading under the name Bio Gold, has received $288,500 in Government funding through the Ministry for Primary Industries' Sustainable Food and Fibre Futures fund (SFF Futures) to lay the foundations for a pine pollen industry in New Zealand.

"Pine pollen has been consumed for health and wellbeing in China, South Korea and Japan for more than 3000 years," Bio Gold founder Carl Meyer said.

"It's been found to contain a naturally occurring testosterone, and lately there's been a new wave of interest from the natural health industry in the United States and Canada."

Common reasons for taking pine pollen as a dietary supplement include supporting energy levels, hormonal balance, immune function, and overall wellbeing.

"We've furthered our research and development work for the past 18 months with the help of SFF Futures funding to understand how the biochemistry of New Zealand pine pollen differs in relation to factors such as species, genetics, location, and more," Meyer said.

"We've also compared our pollen to that from overseas and it's looking very promising."

Pine pollen is the fine yellow powder released by pine trees every spring that forms part of the reproductive life cycle of the tree.

The powder is produced inside the catkin (male flowers) of pine trees.

"We've spent years working out which specific type of Pinus radiata yields the best pollen it's not a matter of using any old pine tree," Meyer said.

"It's very complex, and you've got to really know what you're doing. Safety and quality are our top priorities."

Meyer said the final product was expensive because the seasonal window for pine pollen was often less than three weeks.

Bio Gold's pollen was currently harvested near Hanmer Springs and Kaikura from trees on land owned and operated by Ngi Tahu Forestry, he said.

"However, we're also open to exploring additional partnerships with other forest owners across New Zealand, as well as connecting with entrepreneurs, investors, and health companies to help scale things up. We encourage people to reach out to us.

Callaghan Innovation had helped with research, including providing funding for a top Master's student to investigate biochemistry and extraction on an even deeper level, Meyer said.

"The University of Canterbury has also assisted with harvesting trials, and we're developing technology that's able to do large-scale harvesting."

Bio Gold has developed two prototype products so far.

One is a concentrated liquid "Supercharge" extract to support energy levels, sports and exercise performance, libido, and vitality.

The other is a raw powder that can be added to smoothies and drinks for overall wellbeing.

"Establishing this industry means New Zealanders will be able to enjoy any benefits that pine pollen offers," Meyer said.

"Our local customers love the pollen, and we're getting excellent feedback from them. We're also looking at high-value export opportunities."

Steve Penno, MPI's director of investment programmes, said Bio Gold had identified an opportunity to increase the value of New Zealand's forestry industry, and create new jobs in regional communities.

"Investing in this high-value product is helping Bio Gold fast-track their research and take this initiative to a full-scale operation."

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Plant-based testosterone in pine pollen could be a goldmine for forestry - New Zealand Herald

Biochemistry

Researchers Develop Next-Gen Cancer Therapy – University of Houston

Oncolytic viruses are those that can kill cancer cells while leaving nearby healthy cells and tissues intact. Image of cancer cells courtesy: GettyImages

Shaun Zhang, director of the Center for Nuclear Receptors and Cell Signaling at the University of Houston and M.D. Anderson Professor in the Department of Biology & Biochemistry, has created a new oncolytic virus, pushing oncolytic cancer therapy forward.

Among the most promising anti-cancer treatments in recent years, oncolytic virotherapy (OV) has emerged at the top of the pack of immunotherapy. Oncolytic viruses are those that can kill cancer cells while leaving nearby healthy cells and tissues intact. In oncolytic virotherapy, the treatment also exerts its influence by activating an antitumor immune response made of immune cells such as natural killer (NK) cells.

But sometimes those natural killers limit the oncolytic viruses, and so despite the exciting development in the OV field in recent years, there is room for improvement to tackle some limitations, including the relatively weak therapeutic activity and lack of means for effective systemic delivery.

Those improvements are now being made in the lab of Shaun Zhang, director of the Center for Nuclear Receptors and Cell Signaling at the University of Houston and M.D. Anderson Professor in the Department of Biology & Biochemistry. Zhang has received a $1.8 million grant from the National Institutes of Health to support his work.

We have developed a novel strategy that not only can prevent NK cells from clearing the administered oncolytic virus, but also goes one step further by guiding them to attack tumor cells. We took an entirely different approach to create this oncolytic virotherapy by deleting a region of the gene which has been shown to activate the signaling pathway that enables the virus to replicate in normal cells, said Zhang.

The different approach consists of Zhangs lab creating a new oncolytic virus called FusOn-H2, based on the Herpes simplex 2 virus, (HSV-2, commonly known as genital herpes). Its the first of its kind. They arm the virus with a NK cell engager, resulting in what Zhang calls the two birds with one stone strategy to enhance therapeutic effect of the new oncolytic virus. This engager forms a bridge between NK cells and tumor cells, resulting in the killing of the engaged tumor cells.

Our recent studies showed that arming FusOn-H2 with a chimeric NK engager (C-NK-E) that can engage the infiltrated natural killer cells with tumor cells could significantly enhance the effectiveness of this virotherapy, said Zhang. Most importantly, we observed that tumor destruction by the joint effect of the direct oncolysis and the engaged NK cells led to a measurable elicitation of neoantigen-specific antitumor immunity.

Zhang and team believe that this armed FusOn-H2 will produce a three-pronged effect to enhance the antitumor efficacy against solid tumors in colon and lung cancer, which they expect to come in waves.

The first wave comes immediately after the armed virus is administered and it derives primarily from administration of the virus. The second wave comes from the natural killer cells doing their work while the third wave is the outcome of a series of chain events that ultimately result in inducing neoantigen-specific antitumor immunity.

We hypothesize that the combination of the high potency of the three-pronged therapy with the improved systemic delivery will lead to effective treatment of metastatic diseases, said Zhang.

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Researchers Develop Next-Gen Cancer Therapy - University of Houston

Biochemistry

Researchers use rapid antibody test to gauge immune response to SARS-CoV-2 variants – University of Toronto

COVID-19 infections are once again on the rise as our immune systems struggle to combat new variants.

Thats according to a University of Toronto study that foundthe antibodies generated by people who were vaccinated and/or recovered from COVID-19prior to 2022 failed to neutralize the variants circulating today.

Furthermore, the researchers expect that the antibody test they developed to measure immunity in the studys participants will become a valuable tool for deciding who needs a booster and when,helping to save lives and avoid future lockdowns.

The truth is we dont yet know how frequent our shots should be to prevent infection, saidIgor Stagljar, a professor of biochemistry and molecular geneticsat theDonnelly Centre for Cellular and Biomolecular Research andat the Temerty Faculty of Medicine. To answer these questions, we need rapid, inexpensive and quantitative tests that specifically measure Sars-CoV-2 neutralizing antibodies, which are the ones that prevent infection.

The study was led byStagljarand Shawn Owen, an associate professor of pharmaceutics and pharmaceutical chemistry, at the University of Utah.

The journalNature Communications recentlypublished their findings.

Many antibody tests have been developed over the past two years. But only a few of the authorized ones are designed to monitor neutralizing antibodies, which coat the viral spike protein so that it can no longer bind its receptor and enter cells.

It's an important distinction, as only a fraction of all Sars-CoV-2 antibodies generated during infection are neutralizing. And while most vaccines were specifically designed to produce neutralizing antibodies, its not clear how much protection they give against variants.

Our method, which we named Neu-SATiN, is as accurate as but faster and cheaper than the gold standard, and it can be quickly adapted for new variants as they emerge, Stagljar said.

Neu-SATiN stands forNeutralizationSerologicalAssay based on splitTri-partNanoluciferase, and it is a newer version ofSATiN, which monitors the complete IgG poolthey developed last year.

The development of Neu-SATiN was spearheaded byZhong Yao, a senior research associate in Stagljars lab, and Sun Jin Kim, a post-doctoral researcherin Owens lab, who are the co-first authors on the paper.

The pinprick test is powered by the fluorescent luciferase protein from a deepwater shrimp. It measures the binding between the viral spike protein and its human ACE2 receptor, each of which is attached to a luciferase fragment. The engagement of the spike protein with ACE2 pulls the fragments close, catalyzing reconstitution of the full length luciferasewith a concomitant glow of light captured by the luminometer instrument. When a patients blood sample is added into the mixture, the neutralizing antibodies bind to and mop up all spike protein, while ACE2 remains in unengaged state. Consequentially, the luciferase remains in piecesand the light signal drops. The researchers say the plug-and-play design of the test means it can be adapted to emerging variants by engineering mutations in the spike protein.

The researchers applied Neu-SATiN to blood samples collected from 63 patients with different histories of COVID-19 and vaccinationup to November 2021. Patient neutralizing capacity was assessed against the original Wuhan strainand the following variants:Alpha, Beta, Gamma, Delta and Omicron.

We thought it would be important to monitor people that have been vaccinated to see if they still have protection and how long it lasts, said Owen, who did his post-doctoral training in the Donnelly Centre with distinguished bioengineer and University Professor Molly Shoichet of the Faculty of Applied Science & Engineering.But we also wanted to see if you were vaccinated against one variant, does it protect you against another variant?

The neutralizing antibodies were found to last about three to four months beforetheir levels would drop by about 70 per cent irrespective of infection or vaccination status. Hybrid immunity, acquired through both infection and vaccination, produced higher antibody levels at first, but these too dropped significantly four months later.

Most worryingly, infection and/or vaccination provided good protection against the previous variants, but not Omicronor its sub-variantsBA.4 and BA.5.

The data match those from arecent U.K. study thatshowed that both neutralizing antibodies and cellular immunity a type of immunity provided by memory T cellsfrom either infection, vaccination, or both, offered no protection from catching Omicron. In a surprising twist, the U.K. group also found that infections with Omicron boosted immunity against earlier strains, but not against Omicron itselffor reasons that remain unclear.

It's important to stress that vaccines still confer significant protection from severe disease and death, said Stagljar. Still, he added that the findings from his team and others call for vigilance in the coming periodgiven that the more transmissible BA.4 and BA.5 sub-variants can escape immunity acquired from earlier infections with Omicron, as attested by rising reinfections.

There will be new variants in the near future for sure, Stagljar said. Monitoring and boosting immunity with respect to circulating variants will become increasingly important and our method could play a key role in this since it is fast, accurate, quantitative and cheap.

He is already collaborating with the Canadian vaccine maker Medicago to help determine the efficacy of their candidates against Omicron and its sub-variants.Meanwhile, U of T is negotiating to license Neu-SATiN to a company which will scale it up for real world usessuch as population immunosurveillance and vaccine development.

The research was supported with funding from the Toronto COVID-19 Action Fund,Division of the Vice-President, Research & Innovation and the 3i Initiative at the University of Utah.

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Researchers use rapid antibody test to gauge immune response to SARS-CoV-2 variants - University of Toronto

Biochemistry

Clemson research could advance key understanding of cell mutation, pave way to new cancer treatments – Greenville Journal

A number of Clemson University research projects are designed to advance critical understanding of how cancer cells function, but one project seeks to unlock some of the mysteries behind the most common type of cancer and lead to more effective treatments.

Jennifer Mason, assistant professor of genetics and biochemistry and a researcher in Clemsons Center for Human Genetics, has received more than $2.6 million in grant funding to investigate how cells repair DNA damage and what happens when those processes go wrong.

Such breakdowns can lead to mutations, according to Mason, a process at the heart of most cancers and increasingly tied to many diseases. Her research aims to answer many important questions about a particular DNA repair protein, known as FBH1, tied to the most common form of cancer, skin cancer, and its most deadly variant, melanoma.

Cancer is a disease of mutation, Mason says. The majority of cancers have an underlying defect that causes the cells to increase their mutation rate.

Masons work is being funded in part by a $792,000 research scholar grant from the American Cancer Society. Her research was inspired by a study that found missing or defective FBH1 in a majority of melanoma cases.

DNA damage is a natural process that happens in human cells, and one of the most common causes of such damage is ultraviolet light from exposure to sunlight. UV light is a major cause for melanoma, according to the American Cancer Society, and states with a high UV index, like South Carolina, tend to have higher incidences of melanoma in their populations.

Among the aims of Masons research is to find out why missing or defective FBH1 is resistant to DNA-destroying compounds, a property at the heart of most chemotherapies. Cracking that puzzle could lead to more effective cancer treatments.

Thats the hope of where someday this research will lead, she says.

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Clemson research could advance key understanding of cell mutation, pave way to new cancer treatments - Greenville Journal

Biochemistry

Dihydropyridine (DHP) Market Insights 2022 And Analysis By Top Keyplayers Shenzhen Simeiquan Biotechnology, Boc Sciences, Weifang Union Biochemistry,…

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Biochemistry

University of Utah Health Biochemist Matt Miller Named Pew Scholar – University of Utah Health Care

Jun 14, 2022 8:00 AM

Matthew Miller, Ph.D., an assistant professor of biochemistry at University of Utah Health, was named as a 2022 Pew Scholar for his exploration of the cellular machines that help accurately divide and separate chromosomes during cell division. This work is critical as even the smallest errors in this process can have harmful consequences, including birth defects, miscarriages, and cancer.

Miller is one of 22 scientists nationwide to receive the honor from the Pew Charitable Trusts. The Pew Scholars Program in the Biomedical Sciences provides funding to early-career investigators of outstanding promise in science that is relevant to the advancement of human health.

Millers research focuses on a key phase of cell division, or mitosis, when protein-based machines called kinetochores help chromosomes correctly maneuver between parent and newly forming daughter cells. This process ensures that each cell receives a complete set of accurately replicated chromosomes.

Better understanding of how kinetochores work could lead to the development of genetic interventions or other treatments to reduce the risk of these disorders, Miller says.

Matt Miller is studying a truly fascinating and red-hot area of research, says Wes Sundquist, Ph.D., a former Pew Scholar and chair of the Department of Biochemistry at the University of Utah Health. To address this problem, Matt uses an amazingmulti-disciplinary combination of biochemistry, biophysics, genetics, and cell biology for which he is almost uniquely qualified owing to his wonderful breadth, insight, and creativity.

Understanding the process of chromosome separation during mitosis is a difficult challenge, according to Miller. Thats because of its dynamic nature and the inability to precisely replicate the physical forces that regulate these activities in cells.

To overcome this difficulty, Miller and his colleagues purify the protein machines involved and have developed techniques which allow them to reestablish their complex activities outside of a cell. This allows the researchers to experimentally control things such as applied physical force and ultimately understand how these factors carry out this process so reliably.

Kinetochores are incredible protein machines, Miller says. They move chromosomes within an ever-changing environment and are signaling hubs that help regulate the cell cycle. Biologists have been fascinated with this process for more than 100 years, yet we still dont know how kinetochores achieve their remarkable feats.

In fact, according to Miller, scientists still dont have a complete parts list for the inner workings of kinetochores. Its like knowing that an internal combustion engine makes a car run but not understanding that under the hood it is a collection of pistons, spark plugs, and other vital moving parts, he says.

Despite this, Miller and his colleagues are unraveling several key aspects of kinetochores and their role in cell division.

During cell division, the cells genetic information, or DNA, is packaged into structures known as chromosomes, which need to be copied and then partitioned equally between resulting daughter cells. To facilitate this process, kinetochores assemble on chromosomes and attach themselves to the mitotic spindle, a molecular machine that forms thin, thread-like strands called microtubules. Once they do this, the duplicated chromosomes can move to opposite ends of the parent cell in preparation for cell division.

If kinetochores dont do their job correctly, then the chromosomes wont divide evenly, and one cell could end up with too many or too few of them. As a result, harmful imbalances and mutations can occur, Miller says.

Fortunately, these types of errors are rare. So what keeps the chromosomes attached to the right microtubules? It all boils down to tension, Miller says.

To accurately segregate replicated chromosomes to daughter cells, the chromosome must attach to microtubules from opposite sides of the cell. This pulling from opposite sides generates tension, telling the cell it has the correct attachment configuration and can proceed with cell division. Miller and colleagues recently discovered that kinetochores have an intrinsic mechanism that senses this tension. It acts, Miller says, like a childs finger trap, a simple puzzle that traps fingers in both ends of a small cylinder woven from bamboo. The harder a person tries to pull their fingers out, the tighter the device gets.

In much the same way, the tension created by the force of opposing microtubule pulling keeps the chromosomes aligned properly. When the kinetochores sense the right amount of tension, they give the go-ahead signal and then move each of their chromosomes to opposite sides of the parent cell, enabling accurate cell division.

Using an array of cutting-edge tools in biochemistry, biophysics, and gene editing, Miller hopes to determine which parts of the protein machines are responsible forchromosomal attachment and segregation.

We will then reconstitute the activities of these protein machines in a test tube to discover the mechanisms these protein machines use to carry out this process, Miller says. This work could lead to novel strategies for reducing the chromosomal segregation defects that give rise to many human diseases, including cancer and developmental disorders such as Down syndrome.

The 2022 class of Pew scholarsall early-career, junior facultywill receive four years of funding to explore some of the most pressing questions in health and medicine. They were chosen from 197 applicants nominated by leading academic institutions and researchers across the United States.

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Research News Biochemistry Pew Scholar

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University of Utah Health Biochemist Matt Miller Named Pew Scholar - University of Utah Health Care