Lab News Archive : The Ott Lab

Reflections on a Pandemic: 6 Questions with Melanie Ott

Earlier this year, the World Health Organization declared an end to the global health emergency for COVID-19. This announcement was quickly followed by the US federal government’s plan to end its own public health emergency declaration for the SARS-CoV-2 virus.

Of course, SARS-CoV-2 is still with us. It is also a matter of when, not if, the next pandemic will emerge. These realities mean that the research advances made by Gladstone scientists over the last three years will continue to impact efforts against existing and new viruses for years to come.

Melanie Ott, MD, PhD, director of the Gladstone Institute of Virology (GIV), reflects on the early days of the pandemic, her team’s biggest contributions to COVID-19 research, and the new directions they are taking to understand the underlying biology of viruses, including coronaviruses and HIV.

Inside long COVID’s war on the body: Researchers are trying to find out whether the virus has the potential to cause cancer

Long COVID is no stranger to either patients or those immersed in studies of its effects. In the U.S., one in 7 adults–about 14% of the adult population–has experienced symptoms that lasted three months or longer after first contracting the virus. The worldwide estimate for long COVID is 65 million people.

What is less clear–because it’s still so early in the process–is the impact of some of SARS-CoV-2’s most dangerous characteristics on those hit by long COVID. But some researchers are warily watching for the worst: a potential connection to cancer.

No such connection has been established, and the process of learning whether there is one–and to what extent–will rightfully take years. The experts who spoke with me cautioned that most of what they are considering is hypothetical, and the National Cancer Institute did not respond to multiple interview requests.

When Two Disruptive Technologies Converge

Here’s the future: a doctor takes a blood sample from her sick patient. In the lab down the hallway, scientists reset the patient’s blood cells into a developmental blank slate using a cocktail of chemicals. Then, they add a combination of tiny molecules that edit the cells’ DNA. Perhaps this editing process repairs a disease-causing mutation or gives the cells a new ability to ward off infection, inflammation, or cancer. Finally, the embryo-like cells are grown into healthy, adult cells—heart cells to quell heart disease, brain cells to treat Alzheimer’s, or immune cells to shrink a tumor—and infused back into the patient’s body. Or perhaps, the doctor infuses the specially designed molecules that edit cells’ DNA right into the patient, and corrections are made directly inside their body.

Meet Gladstone: Mir Khalid

Born and raised in Bangladesh, Mir Khalid (he/him) is a scientist in Melanie Ott’s lab at Gladstone Institutes. He completed his bachelors and master’s in genetic engineering and biotechnology at the University of Dhaka, Bangladesh. He completed a master’s in infection and immunity at Erasmus University in Rotterdam, Netherlands. He performed his PhD research in the Ott lab studying molecular virology, and received his degree from Erasmus University.

How Understanding RNA Structure Can Help Researchers Design Better HIV Drugs

To spread between cells in the body and hop from person to person, human immunodeficiency virus (HIV) must copy its genetic material, produce viral proteins, and assemble new virus particles. For this complex process to occur, a viral protein called Tat must bind to a section of the virus’s RNA—the molecules that carry instructions for making new proteins—which is called the HIV trans-activation response element (TAR).

The TAR RNA can assume many different shapes, known as conformations. However, the Tat protein can only bind to one of these conformations, and if TAR is in a conformation that does not bind to Tat, HIV won’t replicate. So, understanding how these molecules interact could help scientists design therapies that block HIV replication.

How Zika virus prevents normal brain development once neural progenitor cells are infected

When Zika virus crosses the placenta to infect a foetus in a pregnant woman, it attacks life before it’s had a chance to establish itself, like squashing a seed before planting it. In particular, the virus infects starter cells for the nervous system, neural progenitor cells, thus causing wide-reaching developmental problems down the line. To investigate how these impacts take hold, researchers examined these cells in the lab, and focused on a protein called UPF1, which manages mRNA – transcripts of genes being expressed. Infected cells have less UPF1 and the researchers saw that as a result, transcripts (red) become stuck in the cell nucleus (blue) in cells infected with Zika (green, right), compared to uninfected (left). This reduces the production of proteins from those transcripts, such as one called FREM2, required to maintain and determine the identity of neural progenitor cells, and so hinders healthy development from the start.

Fall’s COVID Shots May Be Different in One Key Way

This year’s might include XBB.1 and … perhaps no other strain.

This fall, millions of Americans might be lining up for yet another kind of COVID vaccine: their first-ever dose that lacks the strain that ignited the pandemic more than three and a half years ago. Unlike the current, bivalent vaccine, which guards against two variants at once, the next one could, like the first version of the shot, have only one main ingredient—the spike protein of the XBB.1 lineage of the Omicron variant, the globe’s current dominant clade.

That plan isn’t yet set. The FDA still has to convene a panel of experts, then is expected to make a final call on autumn’s recipe next month. But several experts told me they hope the agency follows the recent recommendation of a World Health Organization advisory group and focuses the next vaccine only on the strains now circulating.

InvisiShield Technologies Collaborates with Gladstone Institutes to Accelerate Development of Intranasal Preventatives against SARS-CoV-2, Influenza, and RSV

InvisiShield Technologies Ltd., a pre-clinical-stage biotechnology company focused on developing intranasal preventives for major disease-causing respiratory viruses, today announced a collaboration with Gladstone Institutes to develop intranasal preventatives against airborne infection, including SARS-CoV-2, influenza, and respiratory syncytial virus (RSV).

Gladstone Institutes, a non-profit biomedical research organization that uses visionary science and technology to overcome disease, will leverage its expertise in immunology and virology to support the collaboration. Gladstone has made significant contributions to better understanding and developing new therapies for a range of viral diseases, including HIV/AIDS and COVID-19.

The collaboration aims to develop intranasal preventatives that can protect individuals from viral infections, including SARS-CoV-2, the virus that causes COVID-19, as well as influenza and RSV. Intranasal preventatives have the potential to serve as an immediate line of defense against viral infections, irrespective of an individual’s vaccination or immune system status, by targeting the nose and upper respiratory tract where most infections originate.

Tips from Virologists to Face the “Tripledemic” This Holiday Season

As we approach the height of the holiday season, some medical experts have warned of a potential “tripledemic”—a simultaneous surge in cases of COVID-19, the flu, and RSV (respiratory syncytial virus).

How concerned should you be, and what does this mean for your holiday plans?

We asked three Gladstone virologists—Senior Investigator Warner Greene, MD, PhD; Director of the Gladstone Institute of Virology Melanie Ott, MD, PhD; and Senior Investigator Nadia Roan, PhD—for their perspectives.

Medical Milestones are Underway at San Francisco’s Gladstone Institutes

When California shut down in March 2020 and many San Franciscans stayed at home, obsessively ordering hand sanitizer, a group of local scientists pivoted from the projects they were working on and poured all their energy into COVID-19. Jennifer Doudna, PhD, and Melanie Ott, MD, PhD, developed a new testing device, using the gene-editing tool CRISPR, that’s as accurate as a PCR test but can provide rapid results at home (it should hit the market next year). And Leor Weinberger, PhD, developed a nasal spray that people can use after they’ve been exposed to COVID, to disrupt the virus’s ability to spread in the body (clinical trials could begin next year).

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