MSI Analysis and the Application of Therapies Based on 2018 Nobel Immuno-Oncology Work

The 2018 Nobel Prize in Physiology and Medicine was awarded to James P. Allison of the United States and Tasuku Honjo of Japan for their work to identify pathways in the immune system that can be used to attack cancer cells (1). Although immunotherapy for cancer has been a goal for many decades, Dr. Allison and Dr. Honjo succeeded through their manipulation of “checkpoint inhibitor” pathways to target cancer cells.

Immune checkpoint inhibitor drugs have been effective in cancers such as aggressive metastatic melanoma, some lung cancers, kidney, bladder and head and neck cancers. These therapies have succeeded in pushing many aggressive cancers below detectable limits, though these cases are notably not relapse-free or necessarily “cured” (2,3).

One challenge in implementing immunotherapy in a cancer treatment regime is the need to understand the genetic makeup of the tumor. Certain tumors, with specific genetic features, are far more likely to respond to immune checkpoint therapy than others. For this reason, Microsatellite Instability (MSI) analysis has become an increasingly relevant tool in genetic and immuno-oncology research.

What is MSI Analysis?

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Is MPS right for your forensics lab?

Today’s post was written by guest blogger Anupama Gopalakrishnan, Global Product Manager for the Genetic Identity group at Promega. 

Next-generation sequencing (NGS), or massively parallel sequencing (MPS), is a powerful tool for genomic research. This high-throughput technology is fast and accessible—you can acquire a robust data set from a single run. While NGS systems are widely used in evolutionary biology and genetics, there is a window of opportunity for adoption of this technology in the forensic sciences.

Currently, the gold standard is capillary electrophoresis (CE)-based technologies to analyze short tandem repeats (STR). These systems continue to evolve with increasing sensitivity, robustness and inhibitor tolerance by the introduction of probabilistic genotyping in data analysis—all with a combined goal of extracting maximum identity information from low quantity challenging samples. However, obtaining profiles from these samples and the interpretation of mixture samples continue to pose challenges.

MPS systems enable simultaneous analysis of forensically relevant genetic markers to improve efficiency, capacity and resolution—with the ability to generate results on nearly 10-fold more genetic loci than the current technology. What samples would truly benefit from MPS? Mixture samples, undoubtedly. The benefit of MPS is also exemplified in cases where the samples are highly degraded or the only samples available are teeth, bones and hairs without a follicle. By adding a sequencing component to the allele length component of CE technology, MPS resolves the current greatest challenges in forensic DNA analysis—namely identifying allele sharing between contributors and PCR artifacts, such as stutter. Additionally, single nucleotide polymorphisms in flanking sequence of the repeat sequence can identify additional alleles contributing to discrimination power. For example, sequencing of Y chromosome loci can help distinguish between mixed male samples from the same paternal lineage and therefore, provide valuable information in decoding mixtures that contain more than one male contributor. Also, since MPS technology is not limited by real-estate, all primers in a MPS system can target small loci maximizing the probability of obtaining a usable profile from degraded DNA typical of challenging samples. Continue reading

From Drug Screening to Agriculture to Cardiac Development, Dual Luciferase Reporters Bring You the Story

Today’s blog was written by guest blogger Katarzyna Dubiel, marketing intern in Cellular Analysis and Proteomics.

Reporter gene assays have been critical for the study of a wide-range of biological questions, from regulation of gene expression to cellular signaling. While reporter gene assays constitute a large group of technologies, here we highlight the diversity of new discoveries enabled by highly quantitative and easily measured bioluminescent luciferase-based reporter assays. Below are our top picks of exciting research discoveries involving the Dual-Luciferase Reporter Assay format using firefly and Renilla luciferases. Continue reading

Musings on the 2018 International Forum on Consciousness

Held May 2018, Means and Metrics for Detecting and Measuring Consciousness was designed to explore emerging technologies for studying the phenomenon of consciousness, including research related to sleep, wakefulness, altered states, focused attention and coma.  We asked the question: How might our ability to better measure consciousness create opportunities to improve human function, resolve disease states and keep the mind and brain throughput all stages of life?

We’re grateful for the ideas and insights, the personal stories, shared by Christof Koch, Melanie Boly, Franz Vollenweider, Heather Berlin, Nicholas Schiff and Thupten Jinpa, as well as for the sound and movement experiences provided by Lisa O’Connor and Laura Flanagan.  (Videos of their talks can easily be accessed on-line: https://www.btci.org/events-symposia-2018/international-forum-on-consciousness/archive/2018-videos-2/ )

Our sense is that those who joined us (250+ attendees) left both more knowledgeable and inspired.  Comments from participants illustrate their appreciation for presenters’ insights: Continue reading

Kicking Off Summer with Some Cookout Favorites

In the United States, the last Monday of May is Memorial Day, a national holiday in which we honor those who have given their lives in service to the country. For those of us living in Wisconsin, Memorial Day is also usually preceded by the first truly warm weekend of summer. So as families remember their loved ones, they gather together to create new memories in parks and backyards, around picnic tables or on grassy lawns–beginning the summer season of cookouts, picnics and bar-b-ques.

Here at Promega we love a good cookout too. So a few of us have cobbled together some of our favorite summer recipes to share with you. Do you have a favorite summer recipe? Share it in the comments below.  (Please note metric conversions are approximate and have not been tested.) Continue reading

Which DNA Do I Use? How to Choose Your Control and Other DNA Samples

 

DNA double helix molecules and chromosomes.

Today’s Promega Connections blog is written by guest blogger Joliene Lindholm, Promega Technical Services Scientist.

In Promega Technical Services, we are frequently asked questions about choosing among our Human Genomic DNA products. Promega offers DNA that can serve as sources of normal human gene sequences or positive controls where genotype is not critical, and controls for use in genotyping applications like STR analysis. For mouse researchers, we also offer Mouse Genomic DNA. Continue reading

National Optimism Month—Make it a Year

People working togetherToday’s Promega Connections blog is written by guest blogger Tori Sheldon, North America Marketing and Events Coordinator.

It is crazy to think how quickly the months fly by. It feels like yesterday I was watching the ball drop as 2017 turned to 2018. Now it is almost March, when Wisconsin starts to emerge from the cold winter. March also happens to be National Optimism Month.

As I think about optimism, I am reminded of one of the core values that guide interpersonal relationships at Promega: “look for the good, with discernment”.  The spirit of this value is to remember that deep down everyone is trying to come from a positive place and that even though we may not always agree with each other it is an opportunity for further discussion and collaboration.

This value is a part of the Emotional & Social Intelligence (ESI) program at Promega. Continue reading

Adventure in Belize

Today’s blog post is written by guest blogger, Josh Agate, Manager, Global CRM.

Picture from airplane approaching Ambergis Caye

Approaching Ambergis Caye.

Adventure is relative. Most people are looking for new adventures in life, and those can range from planning where to go on vacation to starting a new job. What each person looks for in an adventure and the level of thrill they seek is different. When I learned that Promega had awarded me a trip to a destination of my choice with my family for my job performance, I was excited to plan this new adventure with my wife and two daughters (ages 4 and 6). We decided on a trip to Belize.

The trip required two commercial flights, followed by a puddle jumper flight (with hand-written boarding passes), and a 30 minute boat ride before we arrived at our hotel on the island of Ambergris Caye.  This island, off the northern coast of Belize, would provide the backdrop for our family’s greatest adventure to date. The trip to get to the island wasn’t tedious travel for them; it was a wild ride that included a plane that held 12 people, flying over crystal clear waters and a boat trip, where our hair flew wildly as we were sprayed with ocean mist. Continue reading

Promega Travel Award Blog: An Excursion to Croatia

Dubrovnik, the Pearl of the Adriatic

Dubrovnik, the Pearl of the Adriatic

We invite you to travel with Bettina Bazzini-Lapin, Scientific Client Specialist, who was awarded a Promega Travel Award for sales performance and used her award to travel to Croatia and Italy. In this blog, she describes her travels.

Croatia is an Eastern European country that sits on the Adriatic Sea directly across from Italy. It has more than one thousand islands, and a third of the country is covered by forest. It is known for its beautiful Dalmatian coast line. One of the main sites for travelers to visit is the coastal city of Dubrovnik, known as the Pearl of the Adriatic. This is where my adventure began. Continue reading