Virus-Like Particles: All the Bark, None of the Bite

Globally, there have been over 5 million deaths attributed to COVID-19 since the start of the pandemic. Throughout the ongoing battle against SARS-CoV-2, researchers have been studying the viral lineage and the variants that are emerging as the virus evolves over time. The more opportunities that the virus has to replicate (i.e., the more people it infects), the greater the likelihood that a new variant will emerge.

This short video from the World Health Organization explains how viral variants develop.

The US Centers for Disease Control and Prevention (CDC) classify SARS-CoV-2 variants into four groups: Variants Being Monitored (VBM), Variants of Interest (VOI), Variants of Concern (VOC) and Variants of High Consequence (VOHC). So far, no variants in the US have been identified as VOHC or VOI. Currently, the most common variant in the US is the Delta variant (which includes the B.1.617.2 and AY viral lineages), and it is classified as a VOC.

The Delta variant originated in India and spread rapidly across the UK before making its way into the US (1). Current vaccines, including mRNA and adenoviral vector vaccines, have demonstrated effectiveness against the Delta variant. However, it is a VOC because it is more than twice as contagious as previous variants, and some studies have shown that it is associated with more severe symptoms.

A recent study (2) provides one explanation for the higher infectivity of the Delta variant, using an approach based on virus-like particles (VLPs). The research team was led by Dr. Jennifer Doudna, 2020 Nobel Prize winner for her work on CRISPR-Cas9 gene editing, and Dr. Melanie Ott, director of the Gladstone Institute of Virology at the University of Californiaโ€“Berkeley.

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Writing Successful Grants: Planning Your Budget

This blog is part two of a four-part series on grant writing inspired by resources published by the National Institutes of Health (NIH) and others. 

Your quest for composing and submitting the perfect grant proposal is well underway. You have found your niche and designed your research accordingly. However, you must tread carefullyโ€”you will soon have to endure the next trial: planning your budget.

It is important in any grant application to effectively outline and clarify your budget needs. Any poorly considered aspects of your budget may not reflect well on the overall viability of your proposal, so make sure you provide your reviewers with an accurate description of what resources you will need to accomplish your research goals.

Find your Sweet Spot

A budget that is significantly over or under what would otherwise be reasonable to achieve your goals can undermine reviewersโ€™ confidence in your proposal, as it may seem to them that you donโ€™t fully understand the scope of your research. With your budget proposal, you need to find the range that is just right for youโ€”not too big, and not too small. You will be asked to outline the things that you need to fulfill the aims that you put forth. You should request the money to purchase what you need and provide good justification for your expenses, especially big-ticket items like expensive equipment, as well as personnel.  

Be sure that you carefully review the Funding Opportunity Announcement (FOA) for applicable criteria that you will need to follow in building and planning your budget. There may be limits on the types of expenses you can request, spending caps and overall funding limits. Reviewers will not only determine whether your budget is reasonable, but whether it complies with governing cost principles and other requirements unique to the award for which you are applying.

To learn more, read the NIH article: “Writing a Winning Applicationโ€•Nail your Budget.”

Wants vs. Needs

Take the time to identify those budget items that are necessary to your work and those that are not. As you build out your Specific Aims and design your experiments, your needs will become clear. Make sure that in the process of doing so you seek opportunities to offset cost. Gauge the support that youโ€™ll get from your institution, including resources and funding capacity. You may be able to share equipment, resources and space with other investigators. You should also be prepared for some less obvious expenses like instrument warranty and maintenance costs. If you do need to ask for a high-budget item, be certain that it is a necessity, justify the purchase appropriately, and explain how not having it could impact your project.

Before you ask for money in your application, make sure that what youโ€™re asking for is essential. You should also provide details on the resources that are already available to you. Reviewers will determine whether the costs defined are reasonable given the research aims and methods laid out in your proposal.

Read more about distinguishing your wants versus your needs in this NIH article: “Writing a Winning Applicationโ€•Define Resources.”

Direct vs. Indirect Costs

It is important to understand the difference between direct costs and indirect costs. Direct costs are those expenses that come from your research: salaries, travel, equipment and supplies. Youโ€™ll also be requesting facilities and administrative (F&A) costs, or indirect costs. Examples of indirect costs include payroll, departmental administration and student services, among others. F&A costs are determined by applying your organizationโ€™s negotiated rate to your direct cost base.

The total costs requested in your budget will be allowable direct costs and allowable F&A costs. While you will only need to itemize your direct costs, it is important to understand how both are defined and calculated so you can build a realistic budget with all the key elements accounted for.  

For more about direct versus indirect costs, read this NIH article: “Know the Basics for Facilities and Administrative Costs.”

Your budget deserves careful consideration. The review committee will want to see a budget that strikes the right balance between sensibility and necessity. Take the time to parse out your wants versus your needs and account for all the moving pieces. Your review committee is more likely to approve an application that puts forth a thoughtfully prepared and well-studied budget proposal, which will bring you that much closer to the funding you need.


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How A New Wastewater Surveillance Method Predicted COVID-19 Cases in Italy

Wastewater-based epidemiology (WBE), or sewershed surveillance, is the analysis of wastewater to identify the presence of biologicals or chemicals for the purpose of monitoring public health. In the past, WBE has been used to detect the presence of pharmaceutical or industrial waste, drugs and viruses. Now, it is seen as a valuable tool to monitor COVID-19 outbreaks.

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Writing Successful Grants: Framing Your Research

This blog is part one of a four-part series on grant writing inspired by resources published by the National Institutes of Health (NIH) and others.

Like so many ambitious scientists before, you are setting out on the most perilous of questsโ€•writing a grant proposal. Between your grant and the promise of riches untold lie a series of important tasks that you must complete to win the funding you need. We begin with the piรจce de rรฉsistance of any grant proposal: your research.

Your research is the highlight of your application. It is important to summarize your research well and describe how it will make an impact in your field. You must create a focused hypothesis that can be tested through well-developed aims and experiments, and explain to your review committee where you fit into the larger context of your area of study. Your research is the whole point of your proposal, so itโ€™s important to make it count.

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Celebrating STEM/STEAM Day with UW-Madison’s Cool Science Image Contest

November 8th is National STEM/STEAM Day. For 11 years, the University of Wisconsin-Madison Cool Science Image Contest has celebrated and embraced the art of science. The contest illuminates art in the STEM/STEAM field as students, faculty, and staff submit images and videos that capture science or nature and leave a lasting impression of beauty or wonder. 

This year’s 2021 submissions were created with point-and-shoot digital cameras, cutting-edge microscopes, and both backyard and mountaintop telescopes. Contestants captured the art of science from the massive to the minute. Winning entries showcased animals and plants, the invisibly small structures all around us, and stars and nebulae resting lightyears away from Earth.

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How Can You Improve Protein Digests for Mass Spectrometry Analysis?

Can predigestion with trypisin (ribbon structure shown) improve protein digests for mass spectrometry analysis?
Can pre-digestion with trypsin improve mass spec analysis?

The trypsin protease cleaves proteins on the carboxyterminus of Arginine (Arg) and Lysine (Lys). This cleavage reaction leaves a positive charge on the C-terminus of the resulting peptide, which enhances mass spectrometry analysis (1,2). Because of this advantage, trypsin has become the most commonly used protease for mass spectrometry analysis. Other proteases which cleave differently from trypsin, yielding complementary data are also used in mass spec analysis: these include Asp-N and Glu-C , which cleave acidic residues, and chymotrypsin which cleaves at aromatic residues. The broad spectrum protease, proteinase K is also used for some proteomic analyses. In a recent study, Dau and colleagues investigated whether sequential digestion with trypsin followed by the complementary proteases could improve protein digests for mass spectrometry analysis.

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New Assay to Study SARS-CoV-2 Interaction with Human ACE2 Receptor

Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-associated coronavirus. The most recent version, SARS-CoV-2 was first detected in China in the winter of 2019 and is responsible for the current COVID-19 (coronavirus disease 2019) global pandemic. This virus and its variants have resulted in over 200 million infections and more than 4 million fatalities world-wide. To combat this deadly outbreak the global research community has responded with remarkable swiftness with the development of several vaccines and drug therapies, all produced in record time. In addition to vaccines and drug therapies, diagnostic kits and research reagents continue to roll out to track infections and to help find additional therapies.

This peer-reviewed paper published in Nature Scientific Reports by Alves and colleagues demonstrates how a new assay can be used to discover novel inhibitors that block the binding of SARS-CoV-2 to the human ACE2 receptor as well as study how mutations in the SARS-CoV-2 Spike protein alter its apparent affinity towards human ACE2. The paper also details studies where the assay is used to detect the presence of neutralizing antibodies from both COVID-19 positive samples as well as samples from vaccinated individuals.

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Don’t Dump your Pumpkin! Post-Halloween Uses

Pumpkins have historically been a sure sign of the Halloween season in the United States. Although they are most used for Halloween, there are many ways to use pumpkins after those spooky October days.

Every year in America, more than 1 billion pounds of pumpkin gets tossed in the trash and wasted. Instead of leaving them to rot in the landfill, try one of these ways to get more use out of your pumpkin after this year’s Halloween!

Hopefully, after reading this list, you are able to revel in the fact that a pumpkin is not just for Halloween. Not only can this help you save money, save time, and cook delicious dishes, but it also takes a much more eco-friendly approach instead of wasting food or creating garbage.

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Save Precious Time with Same-Well Multiplexing

Scientist performing a multi-well assay. Same-well multiplexing enables you to look at one event from several perspectives.

A graduate student believes he has mastered the art of โ€œthe assayโ€. No need to run duplicates, he knows exactly which one will get him the answers he needs right away.  

To challenge this, his PI proposes an exercise. He asks of the graduate student, โ€œWhat happens when you treat cells with doxorubicin?โ€

The graduate student raises his cells, treats them accordingly, and decides to run a cell viability assay to determine their fate. He returns to the PI with the final verdict: his cells are dead.

The PI takes a look at the data and asks the graduate student to repeat the experiment with an additional assay for cytotoxicityโ€•but the cytotoxicity assay shows that the cell membranes are intact, which only puzzles the graduate student. The PI asks him to run a third assay for apoptosis, and when the student does so, it becomes clear that the cells are dying.

The PI uses this opportunity to make his point: โ€œNow do you see why I ask for more than one assay?โ€

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Inventory Managment and Onsite Stocking without the Headache

The Helix on-site stocking program has been a resource for scientists for many years. With customized onsite stocking, inventory management and automated billing, losing precious time to a missing reagent is a thing of the past.

Helix freezers and cabinents provide seemless onsite stocking and inventory managment

To better understand the impact of Helix on our customersโ€™ research, we spoke to Chris Thompson of Pro-GeneX, a clinical laboratory in Atlanta, GA. โ€œUsing the Helix system has been a game changer from the first day we got it,โ€ Chris said.  โ€œIt was simple to set up and use from the start and has never let us down.  We routinely show it off to visitors to our lab because we are so impressed with it.  I only wish all my reagents used a system like this.  From an inventory perspective it is the best invention in our lab!โ€

Read our full Q&A with Chris below:

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