Tag Archives: Chemistry

Infection Interruption: Identifying Compounds that Disrupt HIV

Know the enemy

Comparing microbial extracts with Dr. Sandra Loesgen.

The Human Immunodeficiency Virus, or HIV, is the virus that leads to Acquired Immunodeficiency Syndrome (AIDS). Most of our listeners have likely heard about HIV/AIDS because it has been reported in the news since the 1980s, but our listeners might not be familiar with the virus’s biology and treatments that target the virus.

  • HIV follows an infection cycle with these main stages:
    • Attachment – the virus binds to a host cell
    • Fusion – the viral wall fuses with the membrane of the host cell and genetic material from the virus enters the host cell
    • Reverse transcription – RNA from the virus is converted into DNA via viral enzymes
    • Integration – viral DNA joins the genome of the host cell
    • Reproduction – the viral DNA hijacks the host cell activity to produce more viruses and the cycle continues
  • Drug treatments target different stages in the HIV infection cycle to slow down infection
  • However, HIV has adapted to allow mistakes to occur during the reverse transcription stage such that spontaneous mutations change the virus within the host individual, and the virus becomes tolerant to drug treatments over time.

Faulty Machinery

Due to the highly mutable nature of HIV, a constant supply of new drug treatments are necessary to fend off resistance and treat infection. Our guest this week on Inspiration Dissemination, Ross Overacker a PhD candidate in Organic Chemistry, is screening a library of natural and synthetic compounds for their antiviral activity and effectiveness at disrupting HIV. Ross works in a Natural Products Lab under the direction of Dr. Sandra Loesgen. There, Ross and his lab mates (some of whom were on the show recently [1] [2]) test libraries of compounds they have extracted from fungi and bacteria for a range of therapeutic applications. Ross is currently completing his analysis of a synthetic compound that shows promise for interrupting the HIV infection cycle.

“Uncle Ross” giving a tour of the lab stopping to show off the liquid nitrogen.

Working in Lab with liquid nitrogen.

 

 

 

 

 

 

 

Havin’ a blast

Chemistry Club at Washington State University (WSU) initially turned Ross onto chemistry. The club participated in education outreach by presenting chemistry demonstrations at local high schools and club events. Ross and other students would demonstrate exciting chemistry demos such as filling hydrogen balloons with salt compounds resulting in colorful explosions piquing the interest of students and community members alike. Ross originally made a name in

Collecting Winter Chanterelles in the Pacific Northwest.

WSU’s chemistry club, eventually becoming the president, by showing off a “flaming snowball” and tossing it from hand to hand—don’t worry he will explain this on air. For Ross, chemistry is a complicated puzzle that once you work out, all of the pieces fall into place. After a few undergraduate research projects, Ross decided that he wanted to continue research by pursing a PhD in Organic Chemistry at Oregon State University.

 

 

Tune in this Sunday October 7th at 7 PM to hear from Ross about his research and path to graduate school. Not a local listener? Stream the show live or catch this episode on our podcast.

The Mold That Keeps On Giving

All around us, plants, fungi, and bacteria are waging chemical warfare against one another to deter grazing, prevent against infection, or reduce the viability of competitor species. Us humans benefit from this. We use many of these compounds, called secondary metabolites, as antibiotics, medicines, painkillers, toxins, pigments, food additives, and more. We are nowhere close to finding all of these potentially useful compounds, particularly in marine environments where organisms can make very different types of chemicals. Could something as ordinary as a fungus from the sea provide us with the next big cancer breakthrough?

Paige Mandelare with one of the many marine bacteria she works with

Paige Mandelare thinks so. As a fourth-year PhD student working for Dr. Sandra Loesgen in OSU’s Chemistry department, she has extracted and characterized a class of secondary metabolites from a marine fungus, Aspergillus alliaceus, isolated from the tissues of an algae in the Mediterranean Sea. After growing the fungus in the laboratory and preparing an extract from it, she tested the extract on colon cancer and melanoma cell lines. It turned out to be cytotoxic to these cancer cells. Further purification of this mixture revealed three very similar forms of these new compounds they called allianthrones. Once Paige and her research group narrowed down their structures, they published their findings in the Journal of Natural Products.

Next, she grew the fungus on a different salt media, replacing bromine for chlorine. This forced the fungus to produce brominated allianthrones, which have a slightly different activity than the original chlorinated ones. Her lab then sent two of these compounds to the National Cancer Institute, where they were tested on 60 cell lines and found to work most effectively on breast cancers.

The recent publication of Paige in her story of the allianthrones from this marine-derived fungus, Aspergillus alliaceus.Like many organisms that produce them, this wonder mold only makes secondary metabolites when it has to. By stressing it with several different types of media in the lab, Paige is using a technique called metabolomics to see what other useful compounds it could produce. This will also give insight into how the fungus can be engineered to produce particular compounds of interest.

A native Rhode Islander who moved to Florida at the age of ten, Paige has always been fascinated with the ocean and as a child dreamed of becoming a marine biologist and working with marine mammals. She studied biology with a pre-med track as an undergraduate at the University of North Florida before becoming fascinated with chemistry. Not only did this allow her to better appreciate her father’s chemistry PhD better, she joined a natural products research lab where she first learned to conduct fungal chemical assays. Instead of placing her on a pre-med career path, her mentors in the UNF Chemistry department fostered her interest in natural products and quickly put her in touch with Dr. Loesgen here at OSU.

Paige enjoying her time at the Oregon Coast, when she is not in the research lab

After finishing her PhD, Paige hopes to move back east to pursue a career in industry at a pharmaceutical company or startup. In the meantime, when she’s not discovering anticancer agents from marine fungi, she participates in a master swimming class for OSU faculty, trains for triathlons, and is an avid baker.

To hear more about Paige and her research, tune in to KBVR Corvallis 88.7 FM this Sunday July 15th at 7 pm. You can also stream the live interview at kbvr.com/listen, or find it on our podcast next week on Apple Podcasts.