Author: Kari Kenefick

by

Glycobiology Research and Training Opportunities are Plentiful

glycans on cell surface

Artist’s rendering of asymmetrically-branched carbohydrates on cell surface proteins.

Glycobiology is the study of glycans, the carbohydrate molecules that cover the surface of most human cells. Glycans attach to cell surface proteins and lipids, in a process called glycosylation. These cell surface structures are responsible for processes as varied at protein folding, cell signaling and cell-cell recognition, including sperm-egg recognition and immune cell interactions. Glycans play important roles in the red blood cell antigens that distinguish blood types O, A and B.

Opportunities in Glycomics Research
As more is learned about the role of glycans in cell communication, they are becoming important disease research targets, particularly the role of glycans in cancer and inflammatory diseases (2).

Some of the open questions surrounding glycans and glycosylation include glycan structural diversity. While some carbohydrates exist as straight or symmetrically branched chains, those populating the human glycome are asymmetrically branched, making them difficult to create and study in the laboratory (3). Continue reading →

by

What Could You Do with a Faster, More Consistent ADCC Reporter Bioassay?

Fc receptor-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) is an important mechanism of action (MOA) by which antibodies target diseased cells for elimination. Traditional methods for measuring ADCC require primary donor peripheral blood mononuclear cells (PBMCs) or purified natural killer (NK) cells that express Fc receptors on the cell surface. Killing of target cells is an endpoint of this pathway activation and is used in classic ADCC bioassays.

PBMCs and NK cells are notoriously difficult to isolate and culture. Furthermore, cultured cells can be a source of variability.

There is a Better Way

Watch this video to learn why traditional ADCC assays can be problematic. You’ll also learn a solution. Find out how  to not only save time but also reduce assay variability.

For more details on the benefits of working with ADCC Reporter Bioassays go to the product page.

There you’ll see how standardized reagents in Promega ADCC Reporter Bioassays ensure better results and better consistency in an ADCC Reporter Bioassay that saves you time.

by

Quantitating Kinase-Inhibitor Interactions in Live Cells

Kinase target engagement is a new way to study kinase inhibitors for target selectivity, potency and residency. The NanoBRET™ TE Intracellular Kinase Assays enable you to quantitate kinase-inhibitor binding in live cells, making these assays an exciting new tool for kinase drug discovery research.

For today’s blog about NanoBRET™ TE Intracellular Kinase Assay, we feature spokesperson Dr. Matt Robers. Matt is part of Promega’s R & D department and is one of the developers of the NanoBRET™ TE Intracellular Kinase Assay. Continue reading →

by

Could Your Dog Meds End Malaria or Zika Infections?

Mosquito photo

Will the sun soon be setting on dangerous mosquito populations?

Could that once-monthly beef-flavored pill you give your dog to kill fleas and ticks save thousands of human lives in Zika virus- and malaria-infected areas of the world?

That’s the hypothesis examined in a 2018 publication “Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases”, published by Miglianico, et al., in PNAS.

Vector-Borne Diseases Under Siege
Mosquito-transmitted diseases, such as malaria and Zika virus, and sand fly-transmitted leishmaniasis are major causes of mortality in sub-tropical regions. Although with a lower mortality incidence, mosquito-borne West Nile virus has spread in temperate regions such as Europe and the United States. Continue reading →

Factors Influencing Compound Potency in Biochemical and Cellular Assays

Late in 2017, a group here at Promega launched an exciting new assay, the NanoBRET™ Target Engagement (TE) Intracellular Kinase Assay.

It’s easy for me to call this assay exciting; I was an editor on the project team. But judging by the reviews on the SelectScience® web site, others are excited about NanoBRET™ Target Engagement Intracellular Kinase Assay too.

A review of the NanoBRET TE Kinase assay from SelectScience® .

A review of the NanoBRET TE Kinase assay from SelectScience® .

Continue reading →

by

Kinase Drug R & D: Helping Your Inhibitor Make the Cut

Finding the best inhibitor for your kinase doesn’t have to be a long trip.

A recent paper in Journal of Medicinal Chemistry, “Discovery of GDC-0853: A Potent, Selective and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development” (1) details some elegant work in chemical modification and extensive testing during exploration of inhibitors for BTK. As a warmup to the article, here is a brief BTK backstory.

BTK (Bruton Tyrosine Kinase): Importance in Health and Disease 

Bruton’s tyrosine kinase (BTK) was initially identified as a mediator of B-cell receptor signaling in the development and functioning of adaptive immunity. More recent and growing evidence supports an additional role for BTK in mononuclear cells of the innate immune system, especially dendritic cells and macrophages. For example, BTK functions in receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. BTK has recently been identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome (2). Continue reading →

by

Kinase Inhibitors as Therapeutics: A Review

The review “Kinase Inhibitors: the road ahead” was recently published in Nature Reviews Drug Discovery. In it, authors Fleur Ferguson and Nathanael Gray provide an up-to-date look at the “biological processes and disease areas that kinase-targeting small molecules are being developed against”. They note the related challenges and the strategies and technologies being used to efficiently generate highly-optimized kinase inhibitors.

This review describes the state of the art for kinase inhibitor therapeutics. To understand why kinase inhibitors are so important in the development of cancer (and other) therapeutics research, let’s start with the role of kinases in cellular physiology.

The road ahead for kinase inhibitor studies.

Why Kinases? Continue reading →

by

A Surprising New Role for Body Fat?

This cloaked fat cell just might be a superhero.

Forty-some years ago fat was just fat. And it was regarded with disdain, to say the least.

An entire industry existed to help get rid of fat, using what was then the latest mass media technology, television. If you wanted to get rid of fat you could exercise with Jack LaLanne as he worked out on television. We exercised in elementary school PE class to a vinyl recording of “Chicken Fat”. You could strap into a device that employed shaking to get rid of the fat from your “hips”, or eat a piece of chocolate fudge with a hot beverage before meals to curb your appetite.

Fat was not our friend. We knew long before the current diabetes epidemic that being overweight was not good for our health.

Fast forward to the 21st century, where we’ve learned that some forms of fat are actually good for you–important in metabolism, growth and immunity. The variety of types of mammalian fat include brown adipose tissue, beige adipose tissue and white adipose tissue, and it’s possible to convert one to the other under certain conditions. For details on these types of adipose tissue, read this article —after you finish this blog. Continue reading →

by

Black-Footed Ferrets: Back from the Brink

Bff = black footed ferret

Giving some love to a BFF (Black-Footed Ferret).

Today is Valentine’s Day (February 14) and our thoughts turn to doing something special for a significant other (so),  a best friend (bf) or best friend forever (bff).  In this blog we consider doing something special for a bff, but the bff at focus here is not human.

This bff is the black-footed ferret.

That’s correct—we’re talking about the weasel-like critter with the black mask, black tail tip and black feet. This small, wiry animal, with the help of some particularly dedicated humans, has had an amazing come-back story since the 1970s, when these ferrets were believed to be extinct.

About the BFF (Black-Footed Ferret)
The black-footed ferret, Mustela nigripes, is a member of the family Mustelidae, which includes mink, badger, marten, fisher, polecat and wolverine (of course domestic ferrets are also members of this family). Like mink and other members of the mustelidae, bff are long, slender animals that average 18 to 24 inches in length. Black-footed ferrets weigh 1½ –2½ lbs. Female ferrets are “jills”, males are “hobs” and juvenile ferrets are “kits”. The average life span of a black-footed ferret in the wild is 1–3 years. Continue reading →

by

NanoBRET™ Target Engagement Intracellular Kinase Assay Nominated for Scientists’ Choice Award®

Joins Nominees for Best New Drug Discovery & Development Product 2017

SelectScience® nominates NanoBRET™ Target Engagement Kinases Assay as a Best New Drug Discovery & Development product for 2017.

We were honored recently to have NanoBRET™ Target Engagement Intracellular Kinase Assays nominated by SelectScience® as one of the Best New Drug Discovery & Development Products of 2017. This is a Scientists’ Choice Award®, an opportunity for scientists like you worldwide to vote for your favorite new drug discovery/development product.

We are super excited about both the nomination and the NanoBRET™ Target Engagement Intracellular Kinase Assay. Here is a little information about the assay.

Continue reading →