There’s a Microbiome In My Tank!

Imagine a scenario—you’re studying the developmental biology of a species of squid. The squid don’t reproduce in captivity, so females carrying fertilized eggs are collected from the wild and rehomed in your lab’s aquariums. You’ve monitored all the normal aquarium conditions—pH, temperature, salinity—ensuring the animal’s new home mimics its natural environment.

But then, for no reason apparent to you, the clutch of eggs doesn’t develop and doesn’t hatch, derailing your research program until next year when you can collect more adult squid from the wild. What went wrong?

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An Ambitious Endeavor: The Human Proteoform Project

On November 15, 2021, Science Advances announced the launch of The Human Proteoform Project. The ambitious project, led by the Consortium for Top-Down Proteomics, aims to address a critical next step in disease research. This means developing new technologies to outline a complete set of protein forms based on the ~20,000 genes in the human genome.

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Writing Successful Grants: Consider Your Audience

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

You have thoughtfully designed your research and carefully crafted a foolproof budget proposal. Now you come upon the dreaded review committee. But fear not! There are ways to enchant the mysterious reviewer, to reveal their wants and needs and win them to your cause.  

professionals at a workshop; writing successful grants requires understanding your audience

In this blog, we will discuss why considering your audience should be one of your foremost priorities in applying for a grant. You should identify your reviewers and capture their interest through a well-organized and compelling story. If you can effectively frame the intent of your research and successfully communicate how it will benefit your field of study, your chances of completing your quest – or securing funding – can improve ­drastically.

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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 California–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 carefully—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 reviewers’ confidence in your proposal, as it may seem to them that you don’t fully understand the scope of your research. With your budget proposal, you need to find the range that is just right for you—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 Application―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 you’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 you’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 Application―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. You’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 organization’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 quests―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 pièce de résistance 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 it’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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