The Casual Catalyst: Science Conversations and Cafes

There is no shortage of stories about great scientific collaborations that have taken root as the result of an excited conversation between two scientists over sandwiches and beer at a bar or a deli. One of the most famous examples of such a conversation was that between Herbert Boyer and Stanely Cohen when they attended a conference on bacterial plasmids in 1972—that very conversation led to the formation of the biotechnology as the two scientists worked together to clone specific regions of DNA (1).  

“Over hot pastrami and corned beef sandwiches, Herbert Boyer and Stanley Cohen opened the door to genetic engineering and laid the foundations for gene therapy and the biotechnology industry.”  

Steven Johnson, author of Where Do Good Ideas Come From, credits the English coffee house as being crucial to the spread of the enlightenment movement in the 17th and 18th centuries (2). He argues that coffee houses provide a space where ideas can come together and form networks. In fact, he defines the concept of “idea” not as a single entity—a grand thought that poofs into existence upon hard work—but at its simplest level, a new idea is a new network of neurons firing in sync with each other.  

Johnson further argues that the development of great new ideas not only requires a space for ideas to bump into each other, connect and form a network, but also that great ideas are rarely the product of a single “Eureka” moment. Rather, they are slowly developing, churning hunches that have very long incubation periods (2).  

Science is Ripe with “Coffee House” Discoveries

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Cancer Moonshot: Solving Tough Problems

At the American Association for Cancer Research meeting in April 2016, then Vice President of the United States, Joe Biden, revealed the Cancer Moonshot℠ initiative— a program with the goals of accelerating scientific discovery in cancer research, fostering greater collaboration among researchers, and improving the sharing of data (1,2). The Cancer Moonshot is part of the 21st Century Cures Act, which earmarked $1.8 billion for cancer-related initiatives over 7 years.  The National Cancer Institute (NCI) and the Cancer Moonshot program have supported over 70 programs and consortia, and more than 250 research projects.  According to the NCI, the initiative from 2017 to 2021 resulted in over 2,000 publications, 49 clinical trials and more than 30 patent filings. Additionally, the launch of trials.cancer.gov has made information about all cancer research trials accessible to anyone who needs it (3).

“We will build a future where the word ‘cancer’ loses its power.”

First Lady, Dr. Jill Biden

In February 2022, the Biden White House announced a plan to “supercharge the Cancer Moonshot as an essential effort of the Biden-Harris administration” (4).  Biden noted in his address that, in the 25 years following the Nixon administration’s enactment of the National Cancer Act in 1971, significant strides were made in understanding cancer. It is now recognized not as a single disease, but as a collection comprising over 200 distinct diseases. This period also saw the development of new therapies and enhancements in diagnosis. However, despite a reduction in the cancer death rate by more than 25% over the past 25 years, cancer continues to be the second leading cause of death in the United States [4].

The Cancer Moonshot is a holistic attempt to improve access to information, support and patient experiences, while fostering the development of new therapeutics and research approaches to studying cancer. In this article, we will focus on research, diagnostics and drug discovery developments.

Solving for Undruggable Targets

KRAS , a member of the RAS family, has long been described as “undruggable” in large part because it is a small protein with a smooth surface that does not present many places for small molecule drugs to bind. The KRAS protein acts like an off/on switch depending upon whether it has GDP or GTP bound.  KRAS mutations are associated with many cancers including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic ductal adenocarcinoma (PDAC). The G12 position in the protein is the most commonly mutated; G12C accounts for 13% of the mutations at this site, and is the predominant substitution found in NSCLC, while G12D is prevalent in PDAC (5).

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Automated Sampling and Detection of ToBRFV: An Emerging Tomato Virus 

Tomatoes affected by a virus, showing the yellow and brown spots characteristic of ToBRFV.

In the Spring of 2015, greenhouse tomato plants grown in Jordan presented with a mosaic pattern of light and dark green patches on leaves, narrowing leaves, and yellow- and brown-spotted fruit (Salem et al. 2015). The pathogen was identified as a novel plant virus, the tomato brown rugose fruit virus (ToBRFV), and the original outbreak was traced back to the fall of 2014 to Israel (Luria et al. 2017).  This newly emerging virus can infect tomato and pepper plants at any stage of development and greatly affect crop yield and quality. Furthermore, the virus spreads rapidly by mechanical contact but can also be spread over long distances by contaminated seeds (Caruso et al. 2022), and as of 2022 it had been detected in 35 countries across four continents (Zhang et al. 2022).  Compounding its transmissibility, is the ability of the virus escape plant genetic resistance to viral infection (Zhang et al. 2022). There are seven host plants for the virus, including some common grasses and weeds, which could act as a reservoir for the virus, even if it is eliminated from commercial crops. Some researchers consider ToBRFV to be the most serious threat to tomato production in the world. 

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On-site, In-house Environmental Monitoring to Obtain Species-Level Microbial Identification

Loss of life and serious illness from contamination of manufactured products that are consumed as food or used in medical procedures illustrate the need to prevent contamination events rather than merely detect them after the fact.  High-profile news stories have described contamination events in compounding pharmacies (1), food processing and packaging plants (2) and medical device manufacturers (3). Although contamination in manufacturing settings can be physical, chemical, or biological, this article will focus environmental monitoring to determine the quality of a manufacturing facility with respect to microbial contamination.

Scientist in pharmaceutical manufacturing facility  performing environmental monitoring.

To ensure that the products they produce and package are manufactured in a high-quality, contaminant-free environment, many industries are required to establish routine environmental monitoring programs. Samples are collected from all potential sources of contamination in the production environment including air, surfaces, water supplies and people. Routine monitoring is essential to detect trends such as increases in potential pathogens over time or the appearance of new species that have not been seen before so that contamination events can be prevented.

Because environmental monitoring requires identification to the level of the species, most environmental monitoring programs will collect samples and then send them off to a facility to be sequenced for genomic identification of any microbial species. Such genotypic analysis involves DNA sequencing of ribosomal RNA (rRNA) genes to determine the taxonomic classification of bacteria and fungi. In this method, informative sections of the rRNA genes are amplified by PCR; the PCR products sequenced; the sequence is compared to reference libraries; and the results interpreted to make a species-level identification for a given microbial isolate.

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2023 Promega iGEM Grant Winners: Tackling Global Problems with Synthetic Biology Solutions

On June 15, 2023, we announced the winners of the 2023 Promega iGEM grant. Sixty-five teams submitted applications prior to the deadline with projects ranging from creating a biosensor to detect water pollution to solving limitations for CAR-T therapy in solid tumors. The teams are asking tough questions and providing thoughtful answers as they work to tackle global problems with synthetic biology solutions. Unfortunately, we could only award nine grants. Below are summaries of the problems this year’s Promega grant winners are addressing.

UCSC iGEM

An immature night heron against the green surface of Pinto Lake. 2023 Promega iGEM Grant Winner, UCSC iGEM seeks to mitigate these harmful aglal blooms.
A night heron hunts on Pinto Lake, California.

The UCSC iGEM team from the University of California–Santa Cruz is seeking a solution to mitigate the harmful algal blooms caused by Microcystis aeruginosa in Pinto Lake, which is located in the center of a disadvantaged community and is a water source for crop irrigation. By engineering an organism to produce microcystin degrading enzymes found in certain Sphingopyxis bacteria, the goal is to reduce microcystin toxin levels in the water. The project involves isolating the genes of interest, testing their efficacy in E. coli, evaluating enzyme production and product degradation, and ultimately transforming all three genes into a single organism. The approach of in-situ enzyme production offers a potential solution without introducing modified organisms into the environment, as the enzymes naturally degrade over time.

IISc-Bengaluru

Endometriosis is a condition that affects roughly 190 million (10%) women of reproductive age worldwide. Currently, there is no treatment for endometriosis except surgery and hormonal therapy, and both approaches have limitations. The IISc-Bengaluru team at the Indian Institute of Science, Bengaluru, India, received 2023 Promega iGEM grant support to investigate the inflammatory nature of endometriosis by targeting IL-8 (interleukin-8) a cytokine. Research by other groups has snow that targeting IL-8 can reduce endometriotic tissue. This team will be attempting to create an mRNA vaccine to introduce mRNA for antibody against IL-8 into affected tissue. The team is devising a new delivery mechanism using aptides to maximize the delivery of the vaccine to the affected tissues.

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Conversations: Nerve-Tumor Crosstalk in the Tumor Microenvironment

Cancer cells are characterized by features such as metabolic reprogramming and uncontrolled proliferation all of which are supported by underlying genomic instability, inflammation and the tumor microenvironment.

Cancer cells can be distinguished from normal cells by a variety of features including their ability to inappropriately activate signals for cell proliferation, evade growth suppression from contact inhibition or tumor suppressor activity, evade cell death signals, replicate DNA continually, induce angiogenesis, invade new tissues, reprogram their metabolism to provide energy for rapid proliferation, and evade immune detection (1) . Several biological processes are responsible for these features including genomic instability, inflammation, and the creation of a tumor microenvironment.

The tumor microenvironment is the network of non-malignant cells, connective tissue and blood vessels that surround and infiltrate the tumor. These surrounding “normal” cells interact with each other and the cancer cells and are important players in tumorigenesis. One cell type that is often found in the tumor microenvironment are nerve cells. In fact, cancer cells often express proteins that encourage nerve growth into the tumor microenvironment such as growth factors and axon-guidance molecules (2). Crosstalk between nerve cells and tumor cells can facilitate development of several cancer types (2) including pancreatic, head and neck, oral, prostate, and colorectal cancers.

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Avoid the Cloning Blues This Season

I was blasting a holiday music playlist while driving recently, and Presley’s Blue Christmas played. I couldn’t get the phrase “Christmas Cloning Blues” out of my mind, and by the time I arrived at my destination, this happened:

Cloning Blues Christmas

(to the tune of Blue Christmas by Elvis Presley)

Blue and white colonies on a selective plate. Careful planning can help you avoid the cloning blues
Blue/White cloning is a standard technique in molecular biology labs.

I’ll have a blue Christmas without you

Colonies so blue, insert without you

Incubating my plates at 37 degrees

Won’t be the same if you’re not in lacZ


And all those blue colonies are forming

When my lab mates’ clonings are performing

They’ll be doing alright,

With their plates all filled with white

But I’ll have a blue, blue, blue cloning

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A Virus Makes a Comeback: Emerging Poliovirus Transmission in the West

In 1921, at age 39, Franklin D. Roosevelt, the man who would later be elected the 32nd president of the United States, was diagnosed with polio (poliomyelitis). His symptoms included fever, gastrointestinal issues, numbness, and leg and facial paralysis. The disease left him paralyzed from the waist down, relying on a wheelchair and leg braces to walk.

The paralysis from poliovirus infection affected the involuntary muscles that allow breathing, and iron lungs were used to keep patients breathing until they cleared the infection.
The paralysis from poliovirus infection affected the involuntary muscles that allow breathing, and iron lungs were used to keep patients breathing until they cleared the infection.

At the height of the polio epidemic in 1952, more than 3,000 people died of polio in the United States, and 20,000 more people suffered paralysis. Pictures of the era show children in special hospital wards, inside ominous-looking iron lungs, while “recovered” children played on the grounds of hospitals wearing leg braces.

In 1938, Roosevelt founded the March of Dimes, which funded the development of the Salk polio vaccine. Two years after the introduction of the Salk vaccine in 1955, polio cases in the US dropped by 90%. In fact, sustained polio transmission has been absent from the US for nearly 40 years; according to the CDC, the last case of wild poliovirus in the US occurred in 1979.

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Keeping Cool When It Hurts: An Engineered Alternative to Pharmacological Pain Management

Pain management, particularly long-term pain management, is a difficult problem. Opioids are effective at reducing pain, but they are addictive and carry with them the significant costs of addiction and overdose that affect not only the individual but society as well. 

Saltatory conduction in neurons.  Localized cooling of neurons may provide a non-addictive method for pain management.

Recently, work presented in Science by Reeder and colleagues proposes an engineering solution to pain management: miniature, implantable devices that can deliver localized and reversible neural blocking to reduce pain. While such devices could deliver any kind of stimulus ranging from electrical to pharmacological, the researchers developed a device that temporarily blocks neural signals by cooling.

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Designing Better Therapeutic mAbs: An Assay for Rapid, Parallel Screening of Fc/ FcɣR Interactions

The first monoclonal antibody (mAb) was produced in a lab 1975, and the first therapeutic mAb was introduced in the United States to prevent kidney transplant rejection in 1986. The first mAb used in cancer treatment the anti-CD20 mAb, rituximab, was used to treat non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Today therapeutic mAbs have become a mainstay of cancer, autoimmune disease, and metabolic disease therapies and include HERCEPTIN® used to treat certain forms of breast cancer, Prolia used to treat bone loss in post-menopausal women, and Stelara used to treat autoimmune diseases like psoriatic arthritis and severe Crohn disease, among many others. Therapeutic mAbs bind targets with high specificity and affinity and they can recruit effector cells to drive target elimination through mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP), making them highly specific, effective therapies.

3D rendering of a Lumit Assay which can be used  for plate-based screening assay to measure the affinities of Fc interactions of therapeutic mAbs.
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