Questions of Genome Privacy and Protection

In April 2018, law enforcement officials announced the arrest of a suspect in the Golden State Killer case (New York Times ). Shortly after the announcement, those same law enforcement officers explained that detectives had used a public forensic genealogy web site to help identify the killer.

What does it mean when a law enforcement agency accesses a public genetic genealogy database to search for a suspect in a crime? Continue reading

Catalyzing Solutions with Synthetic Biology

Computer-generated model of a virus.

The keynote speaker for this year’s International Symposium on Human Identification (ISHI), Andrew Hessle, describes himself as a catalyst for big projects and ideas (1). In biology, catalysts are enzymes that alter the microenvironment and lower the energy of activation so that a chemical reaction that would proceed anyway happens at a much faster rate—making a reaction actually useful to the biological system in which it occurs.

In practical terms, Andrew Hessel is the person who helps us over our inertia. Instead of waiting for someone else, he sees a problem, gathers an interested group of people with diverse skills and perspectives, creates a microenvironment for these people to interact, and runs with them straight toward the problem. Boom. Reaction started.

One of the problems he has set his mind toward is that of cancer drug development. Continue reading

Orchestrating the Genome: Final Thoughts for #HumanGenomeMonth

Recently I wrote about the completion of the human genome sequencing project and the promise, problems and questions that the project has generated in the last decade and a half. One of the biggest realizations that I had from researching and writing that post is that our human genome makes us more alike than different at the molecular level, yet there is incredible variability in the human species around the globe.

I started to think about other things where the basic building blocks were the same, yet the final products were so very different—and I landed in the middle of a symphony orchestra.

Orchestras, if we look at the instruments that they have at their disposal, are very similar: dare I say 99% identical? For instance the instruments listed in the February 2017 roster for the New York Philharmonic Orchestra on Wikipedia (1) are very similar to the lists of instruments listed for the musicians of the Atlanta Symphony Orchestra on its web site (2). Numbers and groupings might vary, but the instruments are the same.

However no one would argue that the New York Philharmonic Orchestra and the Atlanta Symphony Orchestra and Chorus are interchangeable. Experiencing one is not the same as experiencing the other, and two separate experiences of either are often completely different.

The orchestral “DNA” is the same: highly trained musicians playing essentially the same set of instruments, and quite often the same piece of music. What makes each experience of these organizations unique is the when, the where and the how of the expression of that DNA. Continue reading

The Age of the Genome: Commercial DNA Sequencing, Familial Searching and What We Are Learning

Crowd of people at the street, city center

All of these people are 99% the same at the genomic level. The individuals of the human species are far more alike than different.

There are 3 billion (3,000,000,000) bases in my genome—in each of the cells of my body. Likewise, Johanna, the writer who sits next to me at work also has 3 billion bases in her genome. Furthermore, our genomes are 99% the same. Still, that’s a lot of places where my genome can differ from hers, certainly enough to distinguish her DNA from mine if we were both suspected of stealing cookies from the cookie jar. The power of discrimination is what makes genetic identity using DNA markers such a powerful crime solving tool.

The completion of the human genome project in 2003 ushered in a tremendously fast-paced era of genomics research and technology. Just like computers shrank from expensive, building-filling mainframes to powerful hand-held devices we now call mobile phones, genome sequencing has progressed from floor-to-ceiling capillary electrophoresis units filling an entire building to bench top sequencers sitting in a corner of a lab. The $99 genome is a reality, and it’s in the hands of every consumer willing to spit into a tube.

Commercial DNA sequencing services are promising everything from revealing your true ancestry to determining your likelihood to develop dementia or various cancers. Is this progress and promise or is it something more sinister?

As it turns out, that isn’t an easy question to answer. What is probably true is that whole genome sequencing technologies are being put into the hands of the consumer faster than society understands the ethical implications of making all of this genomic information so readily available. Continue reading

Counting Crows: Evidence for Hard-Wired, Inborn Ability to Detect Numerical Sets

“The Great Book of Nature is written in mathematical language” –Galileo Galilei (1)

carrion crow (corvus corone) headshot portrait against a blue background

Carrion Crow (Corvus corone)

If mathematics is the language of the universe, might we find the ability to do math hard-wired in species?

Research in primates has demonstrated that even without training, humans and monkeys possess numerosity, the ability to assess the number of items in a set (2,3).

A paper in Current Biology from Wagener and colleagues provides evidence that crows are born with a subset of neurons that are “hard wired” to perceive the number of items in a set (4). This work provides yet more evidence supporting a hypothesis of an innate “number sense” that is provided by a specific group of “preprogrammed” neurons.

In this study, Wagener’s group measured the responses of single neurons in two “numerically naïve” crows to color dot arrays. They measured neurons in the endbrain region known as the niopallium caudolaterale (NCL), which is thought to be the avian analog of the primate prefrontal cortex. They found that 12% of the neurons in NCL specifically responded to numbers and that specific neurons responded to specific numbers of items with greater or lesser activity.

This is the first such study to investigate the idea of an innate “sense of number” in untrained vertebrates that are not primates, and as such it suggests that a hard-wired, innate “sense of number” is not a special feature of the complex cerebral cortex of the primate brain but is an adaptive property that evolved independently in the differently structured and evolved end brains of birds.

Many questions remain. Are there similarities in the actual neurons involved? What does learning do on a physiological level to these neurons: Increase their number, increase connections to them?  What other vertebrates have similar innate mechanisms for assessing numbers of items? What about other members of the animal kingdom that need to have a sense of number for social or foraging behavior? How is it accomplished?

And finally, one last burning question, if birds are dinosaurs, does that mean that dinosaurs perished because they didn’t do their math homework? Asking for an eleven-year-old I know.

  1. Tyson, Peter. (2001) Describing Nature with math. NOVA 
  2. Izard, V. et al. (2009) Newborn infants perceive abstract numbers PNAS USA 106, 10382–85.
  3. Viswanahtan, P. and Neider, A. (2013) Neuronal correlates of a visual “sense of number” in primate parietal and prefrontal cortices. PNAS USA 110, 1118–95.
  4. Wagnener, L. et al. (2018) Neurons in the endbrain of numerically naïve crows spontaneously encode visual numerosity Cur. Biol. 28, 1–5.

Get Out and Count: The Great Backyard Bird Count of 2018

2018 has been designated “The Year of the Bird”, and beginning today, Friday, February 16, 2018, bird lovers around the world will grab their binoculars, fill their bird feeders, update their eBird app, and look toward the skies. The 21st Annual Great Backyard Bird Count, one of the largest and longest running citizen science projects, begins today, and you can be part of this grand event of data collection.

All it takes is a mobile device (or computer) to log your results, an account at , and 15 minutes of your time during the four-day event.

Can’t tell a red-tailed hawk from a red-winged black bird? That’s okay. The GBBC web site provides a handy online bird guide.  The web site also provides a guide for tricky bird IDs, including: Which Red Finch is it, Identifying Some Common Sparrows, and Identifying Doves.

I recently spent some time talking to Brian Schneider, one of the educators at the Aldo Leopold Nature Center in Monona, WI, to get some tips for first-time birders. Continue reading

Optimizing Your Scientific Conference Experience

When I was in graduate school (a really long time ago), I remember going to my first big conference—American Society for Cell Biology—and being completely overwhelmed. I walked in with my Annual Conference Proceedings (back then it was all paper—no apps—and those books were thick, heavy and took up a ridiculous amount of space in your luggage). I had highlighted at least 100 posters that I was going to visit, along with one talk at every session that remotely applied to my work. And of course, I was not going to miss a single platform presentation. I was grimly determined to learn everything.

After a day-and-a-half, I was too tired to even troll the exhibition floor for freebies.

In my current job, I spend time monitoring hashtags for scientific conferences, and I occasionally notice a plaintive tweet from a conference attendee awash in a sea of posters and platform presentations—wondering where to start or where to stop.

So I asked our scientists at Promega what their tips are for getting the most out of a conference. Here are our Conference ProTips:

Continue reading

Deubiquitinases: A Backdoor into Undruggable Targets?

Molecular model of the yeast proteasome.

Molecular model of the yeast proteasome.

Ubiquitin modification of a protein directs events such as targeting for proteasomal degradation. Targeting a protein for degradation through ubiquitin modification is one way to regulate the amount of time a signaling protein, such as a kinase or other enzyme, is available to participate in cell signaling events. Deubiquitinases (DUBs) are enzymes that cleave the ubiquitin tags from proteins, and they have been implicated in several diseases, including cancer.

With their roles in the stabilization of proteins involved in cell cycle progression and other critical processes, DUBs are promising targets for small molecule inhibitors, particularly since they may provide a “back door” for targeting otherwise intractable, undruggable proteins by modulating their half lives. However, finding small molecule inhibitors of the ubiquitin proteases to date has not been trivial. Here we highlight two papers describing the identification and characterization of small molecule inhibitors against the DUB USP7. Continue reading

Activating the Inflammasome: A New Tool Brings New Understanding

Innate immunity, the first line of immune defense, uses a system of host pattern recognition receptors (PRRs) to recognize signals of “danger” including invariant pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). These signals in turn recruit and assemble protein complexes called inflammasomes, resulting in the activation of caspase-1, the processing and release of the pro-inflammatory cytokines IL-1ß and IL-18, and the induction of programmed, lytic cell death known as pyroptosis.

Innate immunity and the activity of the inflammasome are critical for successful immunity against a myriad of environmental pathogens. However dysregulation of inflammasome activity is associated with many inflammatory diseases including type 2 diabetes, obesity-induced asthma, and insulin resistance. Recently, aberrant NLRP3 inflammasome activity also has been associated with age-related macular degeneration and Alzheimer disease. Understanding the players and regulators involved in inflammasome activity and regulation may provide additional therapeutic targets for these diseases.

Currently inflammasome activation is monitored using antibody-based techniques such as Western blotting or ELISA’s to detect processed caspase-1 or processed IL-1ß. These techniques are tedious and are only indirect measures of caspase activity. Further, gaining information about kinetics—relating inflammasome assembly, caspase-1 activation and pyroptosis in time—is very difficult using these methods. O’Brien et al. describe a one-step, high-throughput method that enables the direct measurement of caspase-1 activity. The assay can be multiplexed with a fluorescent viability assay, providing information about the timing of cell death and caspase-1 activity from the same sample. Continue reading

Genes to Cells to Genomes: Where Will Your Research Questions Take You?

Award presentation

Dr. Walter Blum wins trip to Promega headquarters as part of Promega Switzerland’s 25th Anniversary celebration.

Walter Blum knew how normal cells worked. He had studied and read about the pathways that regulated cell cycles, growth and development; he saw the cell as an amazingly well programmed, intricate machine. What he wanted to understand was: “Why does a cell become crazy? How does it escape immune system surveillance?”

Last week I had the opportunity to sit down with Dr. Blum, a customer of our Promega Switzerland branch. Dr. Blum won a trip to visit our campus in Madison for a week as part of an anniversary celebration for our Switzerland branch. While here, he got an inside peek at research and manufacturing operations, chatted with our scientists, met with our marketing teams and saw the sights in Madison. We talked about his work and what he learned and is taking back with him from his trip to Madison. Continue reading