Wonders of the Conscious and Unconscious Mind—What I Learned from the International Forum on Consciousness

When Heather Berlin was 5 years old, she realized that, at some point in the future, she was going to die. This disturbed her so much that she couldn’t sleep all night. The next morning, she asked her father where she could store all her thoughts so they could live on after she died. There’s no way to do that, said her physician father. “What can I do to make this happen?” she asked. “Maybe become a psychiatrist?” said her dad. Decades later, she became an Assistant Professor of Psychiatry at Icahn School of Medicine at Mount Sinai. Her research focuses on interactions of the brain and mind, with the goal of treating and preventing psychiatric and neurological disorders.

Dr. Heather Berlin told this story at the International Forum on Consciousness held at the BioPharmaceutical Technology Center Institute in Madison, Wisconsin last week. This annual forum gathers scientists from around the world, all interested in understanding how our conscious and unconscious minds work. This year, the forum focused on the newest research and technology for detecting and measuring consciousness. As someone with limited knowledge in this field, my mind was blown by how much researchers have learned so far about consciousness. (No, we can’t store our thoughts in a box…yet.) Here are a few takeaways: Continue reading

From Dating Apps to In Vitro Fertilization, the Challenges to Saving the Endangered Northern White Rhino

In April of 2017 a profile appeared on the dating app Tinder. Describing himself as “One of a kind”, the poster was 43 years old, not in great physical shape, and yet so sought after he required around the clock body guards. His name was Sudan, and he was the last living male northern white rhino. His keepers at the Ol Pejeta Conservancy in Kenya weren’t expecting Sudan to find love. They were hoping to raise awareness of the species’ dire situation and money for the research and development of an in vitro fertilization (IVF) method for rhinos.

Northern white rhino

With only two remaining, can we save the northern white rhino? © Matt Caldwell / 123RF Stock Photo.

Northern white rhinos used to range over all or parts of Uganda, Sudan, Chad, the Democratic Republic of the Congo and the Central African Republic. In the 1960s there were an estimated 2,360 northern white rhinos left in the wild (1). Civil unrest in the region made conservation difficult, and by 2003 poaching and other pressures had reduced the number of northern white rhinos living in the wild to four individuals living in the Garamba National Park in the Democratic Republic of the Congo. There has been no sign of that wild population since 2007 (2), and they are considered extinct in the wild as of 2008. 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

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

HaloTag Application: Fluorescence Under Stress

diagram illustrating the mechanism of the stress reporterCellular stress is associated with global misfolding and aggregation of the endogenous proteome. Monitoring stress-induced abnormalities remains one of the major technical challenges facing established sensors. Misfolded monomers induced by mild stresses, however, remain largely invisible with current sensors.

In a recent publication (1) Fares and colleagues describe a new sensor based upon a fluorescent molecular rotor that is conjugated to a Halo mutant (AgHalo). In non-stressed cells, the AgHalo sensor remains largely folded, and is fluorescent when misfolded. The fluorescent molecular rotor, when conjugated to purified AgHalo to form the proteome stress sensor, is able to report on urea-induced partially unfolded (misfolded) conformations with a higher fluorescent increase than the previously reported fluorophore-based sensors. Heat-induced misfolding is also effectively monitored by the fluorescence change of the sensor that is based on fluorescent molecular rotor, but not the solvatochromic fluorophore. The unique feature of the fluorescent molecular rotor makes the new generation of the AgHalo proteome sensor more sensitive to misfolded conformations that are primarily induced by mild proteome stress. Further, the new sensor exhibits a higher fluorescence signal when detecting soluble and insoluble protein aggregates that are induced by more severe proteome stress. These data collectively suggest that thermo-labile Halo conjugated with a fluorescent molecular rotor serves as a suitable sensor to detect a wide range of proteome stress conditions.

Literature Cited

Fares, M. et al. (2018) A Molecular Rotor-Based Halo-Tag Ligand Enables a Fluorogenic Proteome Stress Sensor to Detect Protein Misfolding in Mildly Stressed Proteome. Bioconjugate Chem 29, 215–24.

Finding Chinks in the Armor: Cancer’s Need for Metabolites

Illustration of energy metablism in cell.Cancer has been studied for decades by scientists trying to find a vulnerability to exploit and testing compounds to develop as potential drugs. As the “Emperor of All Maladies”, cancer has proven itself to be a wily beast with many varieties of genetic mutations for eluding cellular control, tireless in its ability to divide and spread. In the end, a cancer cell is still a cell and subject to its environment even though cancer does not play by the same rules as the normal cells that exist around it. To be able to grow, a cell needs access to metabolites, molecules needed for building the materials and machinery needed by the cell to function and divide. These requirements also offer potential pathways to target for halting cancer growth and spread.

All cells use glucose to generate ATP, but normal and cancer cells differ in how glucose is converted to ATP. Most cells use glucose in oxidative phosphorylation, but cancer cells use aerobic glycolysis, converting glucose to lactate without oxygen. This Warburg effect (glucose converted to lactate) is a hallmark of cancer cells as they take up glucose at a much higher rate than normal cells. Blocking glucose uptake is one way to target cancer cells. While 2-deoxyglucose (2DG) has been shown to slow glucose uptake in vitro, the compound proved toxic in clinical trials and lower dosages do not seem to be an effective treatment against cancer. While not an ideal drug target, glucose uptake has been helpful in monitoring cancer response to therapies via fluorodeoxyglucose positron emission tomography (FDG-PET). Continue reading

Reflections of a Thankful Former Teacher

Today is the start of Teacher Appreciation Week in the United States, punctuated tomorrow by National Thank a Teacher Day. I used to be on the receiving end of the various expressions of gratitude bestowed upon our educators: platters of brownies or cookies from the Board of Education, free meals from restaurants, discounts at retail stores and, if you were really lucky, maybe a student or two (likely initiated by their parents) would bring a gift card or note.

I would also reflect on the teachers that I was personally thankful for: my elementary teachers through graduate school professors (I still remember most of them by name and, with few exceptions, I received what I needed from all of them to learn and grow), my colleagues (who provided mentorship, support and comradery to me and so much more to their students) and my parents (who taught my earliest and most important lessons).

But now I find myself looking at this annual celebration of teachers from the other side—it has been two years since I became a science writer after nearly a decade of teaching high school science. The transition has completely changed my life in ways I could not have imagined and has also impacted the way I think about educators.

The main impetus for this career change was burnout. I had spent countless early mornings, late nights and weekends grading, planning lessons, completing professional development requirements and simply worrying about what challenges I would face the next morning, week or class period. The pressures of each school year would crescendo to a near breaking point every May, and then be swiftly wiped away by the arrival of summer break.

This cycle seemed inevitable, but I had been conditioned by the cultural narrative about teachers to consider it a tolerable tradeoff to the enviable benefits of teaching: holidays and summers “off”, ending the workday before 4 (even I groaned while typing that), great (read: better than average American, worse than someone with similar level of education and experience) benefits & retirement.

Unfortunately, this wasn’t sustainable for me. Moreover, legislative changes and budget cuts exacerbated the ever-present stress to new levels during my last few years as an educator. The strain was taking a toll on my mental health and my ability to be present with family and friends, especially my children.

In my new position, I have been met with intellectual challenges equal to those I encountered as a teacher but face a manageable amount of stress and few threats to work-life balance. Ending my teaching career was probably one of the best decisions I have ever made for my personal well-being. But despite this newfound joie de vivre, I am left with a feeling of guilt that resurfaces whenever issues I used to be so connected with make their way to the national spotlight.

Two of these have been in the news a lot this year—repercussions from budget cuts to education and gun violence in schools. I shouldered the burden of helping my students’ process school shootings and personally dealing with the reality that I could be in the middle of such a tragedy. Similar to the recent wave of teacher walkouts, budget measures that targeted educators brought me to the state capitol in protest.

Yet, I don’t have to face these issues with the sense of urgency I used to. My guilt is rooted in the fact that being a good teacher required selflessness and I chose to be selfish and leave because I couldn’t meet that expectation. It is perhaps because of this nagging feeling that I now feel a gratitude toward teachers that I didn’t before. I am still thankful to all the teachers in my past, but now my appreciation also extends to those that are and will become the future of education.

This year for Teacher Appreciation Week I want to express special gratitude for all of the teachers who feel the same pressures I did and are able to persist. I admire those of you already in the classroom and know you are putting your students’ needs ahead of your own. I’m grateful for all of you who are studying to become teachers, looking past all of the reasons you shouldn’t go into education and focusing instead on the impact you’ll have on future generations.

At a time when it is increasingly difficult to be optimistic about the future, knowing that there are still teachers willing to fight for themselves and their students gives me all the hope I need. Thank you teachers, this week and every week, for all you do!

Introduction to the Laboratory: A New Workshop in Partnership with the UW-Madison Center for Educational Opportunity

During the week of March 26, 2018, while many students were having fun and relaxing during Spring Break, others were busy doing extra lab work at the BTC Institute.  This four-day workshop was designed to provide an introduction to the molecular biology laboratory for students affiliated with the Center for Educational Opportunity (CeO) on the UW Madison campus.  As noted on its web site: “CeO promotes access to resources, academic achievement and personal growth for students whose parents have not received a four-year degree, students who meet specific federal family income guidelines, and students with documented disabilities.”

It is well known that first-generation college students, women and students of color persist in STEM fields at lower rates than the general population. This interferes with the creation of a diverse STEM talent pool, in turn needed to ensure diverse problem-solving perspectives.

Further, STEM fields are often seen as being stressful, given their competitive learning environments.  This may be especially discouraging for students from racial/ethnic minorities who may not have as many mentors and role models to turn to.

Group photo of attendees

Introduction to the Laboratory attendees

This workshop aimed to give students an experience that would strengthen their skills and confidence as they continue to pursue scientific paths. In addition to laboratory work, students discussed the importance of clear communication in written and oral presentations, were required to work as partners to experience teamwork, and were encouraged to use reflection and lab reporting as ways to internalize what they learned throughout the week. Continue reading

Inspiring the Next Generation of Scientists

A Promega scientist works with a girl scout.

Local girls scouts worked with scientists at Promega to learn how a cell culture facility operates.

My twin daughters are finishing up their 10th-grade year next month, finding themselves smack in the middle of their high school experience, and discussions of classes, colleges and careers are increasing in frequency in my household. (It’s cliché, but I have to say it… Where does the time go?) As the girls begin to ponder their future, my husband and I are encouraging them to gain real-life insight from adults who work in fields they’re curious about. It’s never too early to get a first-hand perspective.

One of my girls has known from a pretty young age that she wants to pursue something in STEM, and likely the “S” in the acronym. Her schedule happened to be open the night a few months ago that one of my Promega colleagues, Senior R&D Scientist Danette Daniels, was speaking on a panel sponsored by the University of Wisconsin – Madison chapter of Graduate Women in Science. My daughter wasn’t sure about how she’d be received as the only high school student in the room, but she agreed to go with me anyway. Besides, I told her, they’re serving pie.

The six women on the panel represented a huge variety of avenues (academic to industry), specialties (biophysics to geology) and professional styles. During introductions, one panelist declared, “I had a job in a lab and was depressed. When I was stuck in a library all day, I was totally excited.” She now works with an organization to recruit more women into STEM fields. The woman sitting beside her runs a research lab and declared, “I love the bench quite a bit, and I don’t want to be in an office reading!” 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