Brazilian University Swatting at Leishmaniasis Parasite

The Medicinal Chemistry Center (CQMED), headquartered at Campinas State University in Brazil, recently started a project in partnership with Promega to develop drugs that can be used against Leishmania. This genus of protozoans is the etiological agent of leishmaniasis, transmitted to humans by sandflies.

Microscopic image of Leishmania parasite
Microscopic image of Leishmania tropica. Credit: Brian E. Keas at Michigan State University.

Leishmaniasis is classified as a neglected tropical disease that mainly affects poor communities. Symptoms include large skin sores and an enlarged spleen. The challenge in developing drugs to treat Leishmania is finding appropriate therapeutic targets. These targets are normally proteins whose inhibition leads to death of the parasite. In addition to pharmaceutical company Eurofarma, whose goal is to develop drugs for Leishmania, Promega was chosen to help solve this problem because of our NanoBRET™ Target Engagement (TE) assay*, a well-established technique for measuring protein interactions. In this assay, NanoLuc® luciferase is attached to the protein of interest, and a fluorescent NanoBRET™ tracer molecule is added to the cells. This produces a BRET signal. When a competing ligand is added, it will displace the tracer molecule, enabling quantification of the strength of the interaction compared to the tracer molecule..

A challenge that researchers will face will be ensuring that the NanoBRET™ tracer reaches the inside of the parasite cells; because Leishmania is an intracellular parasite, molecules need to cross the host cell membrane, the membrane of the vacuole containing the parasites, and the membrane of the parasite itself. Another challenge the slow reproduction of Leishmania within macrophages. On top of that is the fact that the parasite’s metabolism varies depending on its biological cycle, meaning that there could be long periods of time during which a drug’s therapeutic target is not expressed in the cell, during which time the drug would have no effect. The ideal target would be expressed at high levels throughout the cell cycle.

The project is being led by Rafael Couñago, a researcher at CQMED, and Promega scientists Matt Robers and Jean-Luc Vaillaud.

*An earlier version of this blog incorrectly said that these experiments are based on the NanoBRET™ assay using HaloTag® protein.

“The Human Placenta,” or “Why I Love Science Writing”

Have you read last week’s breaking story about the microbiome of the human placenta? Wait, stop, don’t run away to Google it! I’ll tell you all about it – this is a science blog, remember?

I’m asking because as I started reading about the topic in preparation for writing this blog post, I noticed two things. First, as a science writer who tries to stay well-connected with what’s going on in the world of biology research, it would have been nearly impossible for me to avoid this story. I get eight or nine daily digest emails from scientific publications every day, and I think over the course of last week, every single one came with a headline related to the placenta study. (Of course, I read them all. And the Nature study they were based on.)

Second, I noticed that each story I read had a slightly different angle on covering the research. As scientists, we like to believe that science is, well, just science. It’s factual. We pore over the data and reach a conclusion. If we aren’t sure of something, we search the journals. The story, if there is one, is about methods and controls, protocols and reagent quality. However, when information about that research is communicated broadly, outside of the journals, we can get a different impression based on how the author frames their article. Continue reading ““The Human Placenta,” or “Why I Love Science Writing””

Curiosity and Collaboration: A PhD Journey

Concepcion Sanchez-Cid didn’t know she wanted to be a scientist when she was older. She grew up with a love of music and played the violin, but her curiosity and eagerness to learn drove her down the path for a career in biomedical research.

Hear more of Concepcion’s story:

As a Master’s student at the University of Granada, Concepcion studied biotechnology and landed an internship at the Promega Europe Training and Application Lab (PETAL) in France. She worked with the Applications Team to develop protocols for DNA and RNA extraction from soil. When she decided to pursue a PhD, she received a sponsorship from Promega and enrolled as a student at the University of Lyon while also remaining an employee at PETAL.

Concepcion says that the balance between both worlds—academia and industry—provide her with technical skills and a unique support network that has helped shape her PhD thesis work. “Working at a university and a company at the same time…you get very different feedback from people that are very specialized, and they really know what they’re doing, so at the end you integrate everything,” she says. “It’s one of the things I appreciate most about my PhD.”

Continue reading “Curiosity and Collaboration: A PhD Journey”

iGEM Stockholm: Blending Art and Synthetic Biology

On May 13, 2019, twenty-five meters below the streets of Stockholm in a retired nuclear reactor, Nerea Capon and her iGEM team unveiled an artistic fusion of creativity and synthetic biology. The Synthetic Biology Art Exhibition featured works by other iGEM teams and local artists, all presenting their unique reflections on the concepts of synthetic biology. The collection included synthetic skin grown by bacteria, performance art, and even a musical snail that spent the week crawling around a table full of plants.

“They were mind-blowing,” Nerea says a few weeks after the exhibition. “We let them have total freedom to interpret synthetic biology as they would love to, and it was really surprising.” Continue reading “iGEM Stockholm: Blending Art and Synthetic Biology”

Selecting the Right Colony: The Answer is There in Blue and White

Agar plate containing colonies important for research, blue and white.
Agar plate containing colonies important for research.

Ah, the wonders and frustrations of cloning. We’ve all been there. After careful planning, you have created the cloned plasmid containing your DNA sequence of interest, transformed it into bacterial cells and carefully spread those cells on a plate to grow. Now you stand at your bench gazing down at your master piece: a plate full of tiny bacterial colonies. Somewhere inside those cells is your DNA sequence, happily replicating with its plasmid host. But wait – logic tells you that not ALL of those colonies can contain your plasmid.  There must be hundreds of colonies. Which ones have your plasmid? You begin to panic. Visions of yourself old and grey and still screening colonies flash through your mind. At the next bench, your lab-mate is cheerfully selecting colonies to screen. Although there are hundreds of colonies on her plate as well, some are white and some are blue. She is only picking the white colonies. What does she know that you don’t?

Continue reading “Selecting the Right Colony: The Answer is There in Blue and White”

B Cells, T Cells and Now X Cells?

The cause of type 1 diabetes (T1D) is not well understood. What is known is that in T1D, immune cells attack pancreatic islet cells that produce insulin. In addition, insulin is an autoantigen that activates T cells in diabetic persons.

A new discovery by Ahmed et al. could further T1D understanding. These findings are also setting B and T cell paradigms on their ear.

About B Cells and T Cells

Components of the B cell receptor.
Components of the B-cell receptor.Image by CNX OpenStax. Used with permission under Wikimedia Commons.

B cells (B lymphocytes) are part of the cellular immune response. They act by means of surface receptor molecules that are immunoglobulins. These B cell receptors are created by highly variable gene rearrangements that result in a huge variety of these surface immunoglobulin molecules. The beauty of B cell receptors (BCR) lies in the fact that, through random gene rearrangements comes a such large variety of B cell surface receptors, that any foreign antigen that makes its way into the body is recognized and snagged by a B cell receptor.

B cells then internalize, process and present these antigens to T cells. Continue reading “B Cells, T Cells and Now X Cells?”

Announcing the 2019 Promega iGEM Grant Winners

It’s FINALLY time to announce the winners of the 2019 Promega iGEM Grant! We received over 150 applications this year, so picking the top 10 was very tough. As always, we’re impressed by the amazing work iGEM teams are doing in the lab and in their communities. The 10 winners listed below will receive $2,000 in free Promega products.

Good luck to all teams competing in iGEM this year, and congratulations to our winners! Don’t forget that Promega has free technical support for all teams competing in iGEM. Our scientists are excited to help out. You can also check out our iGEM Sponsor page, which has tools and resources to help make your project a success. Continue reading “Announcing the 2019 Promega iGEM Grant Winners”

When Proteins Get Together: Shedding (Blue) Light on Cellular LOV

NanoBRETNo protein is an island. Within a cell, protein-protein interactions (PPIs) are involved in highly regulated and specific pathways that control gene expression and cell signaling. The disruption of PPIs can lead to a variety of disease states, including cancer.

Two general approaches are commonly used to study PPIs. Real-time assays measure PPI activity in live cells using fluorescent or luminescent tags. A second approach includes methods that measure a specific PPI “after the fact”; popular examples include a reporter system, such as the classic yeast two-hybrid system.

Continue reading “When Proteins Get Together: Shedding (Blue) Light on Cellular LOV”

Making Research More Sustainable, One Lab at a Time

Do you love your research job? What if you couldn’t do that work anymore? What if future researchers couldn’t have the opportunity to build from what you have accomplished and feel the same joy you do about their research?

Unfortunately, these may become more than hypotheticals for the next generation of scientists due to the impact humans are having on the earth. Scientific research has an outsized impact on some aspects of our unsustainable use of resources. Academic research buildings can use four times more energy than a typical office building and can be responsible for one-third of all waste generated on campus. So, can you make scientific research more sustainable?

Continue reading “Making Research More Sustainable, One Lab at a Time”

Useful or Useless: Weird Things Packed in Our Evolutionary Suitcase

Genetics are a curious thing. Don’t get me wrong, on paper and in theory, the study and science behind our inheritance completely checks out. However, in practice, it can still be a bit disconcerting to look in the mirror one day and recognize your father’s nose and eyebrows in your own face, or to realize you gesticulate in the same animated fashion as your mother, and sometimes hear her laugh come bubbling out of your own mouth.

More curious still are the structures and behaviors that have been carried throughout evolution to the modern era of humanity, though we are considerably distinguishable from our more primitive ancestors.

And perhaps most curious of all, are the structures we continue to pack along with us, as that have little to no known useful function in the contemporary human body. These features are better known as vestigial structures, and are classically defined as features and behaviors that no longer serve the function and purpose they were designed to perform (in comparison to other creatures with the same parts).

Currently, as I recover from the aftermath of a painful encounter with one of my own vestigial organs, I find myself considering if my late appendix ever did anything much for me, or if it’s only purpose was to lie in wait as a metaphorical ticking time-bomb. Prior to my surprise appendectomy, I hadn’t spared much thought for my appendix, and decided I wanted to honor it’s memory by learning more about it, in addition to several of our other human evolutionary leftovers. Man, I wish I would’ve asked the doctors to hang on to that bad boy for me!

The Evolutionary Junk in Our Trunk

Appendix

The appendix is perhaps the most widely known vestigial organ in the human body of today. If you’ve never seen one, the appendix is a small, pouch-like tube of tissue that juts off the large intestine where the small and large intestines connect. By comparison, in herbivorous vertebrates the appendix is much larger, and functions primarily to aid in the breakdown of cellulose in consumed plants. Today, the appendix is considered a small leftover from one of our plant-eating ancestors. As our diets have changed over time, the role our appendix plays in digestion has declined, leaving plenty of room for speculation regarding what purpose it serves now.

Continue reading “Useful or Useless: Weird Things Packed in Our Evolutionary Suitcase”