Using Tumor-Produced Neoantigens to Treat Lynch Syndrome

Lynch syndrome, named for American physician Dr. Henry T. Lynch, is a hereditary condition that causes a predisposition to several types of cancer, most commonly colorectal but to other types as well, including ovarian, endometrial and stomach cancer. The root of this disorder lies in a genetic defect known as DNA mismatch repair deficiency (or dMMR), which affects the process by which mistakes are repaired when our DNA is copied during cell division. People with Lynch syndrome can have up to an 80% increased lifetime risk of developing colorectal cancer, and are more susceptible to developing colorectal and other types of cancers at an earlier age. Accounting for 3-5% of all colon cancers, Lynch syndrome is an excellent target for preventative treatment, like a vaccine. Research exploring a Lynch syndrome vaccine seeks to harness the body’s innate immune response to target tumor cells and has yielded promising results.

Person receiving a vaccine. Lynch syndrome, a hereditary condition that causes a predisposition to several types of cancer is an excellent target for preventative treatment. Read more about how researchers have recently explored vaccines for Lynch syndrome
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Superior Support to Automate and Scale-Up Your Workflows with Ease

Automating a workflow can be a tedious and challenging process that requires lots of time and resources. A helping hand can make all the difference, as it did for Stephanie Dormand, Molecular Supervisor at UniPath Women’s Health, a diagnostics lab located in Denver, Colorado. 

See how Promega Field Service Support staff helped one laboratory automate and scale-up sample processing to improve laboratory workflow. Promega Scientist at a liquid handler.

The women’s health molecular testing service at UniPath primarily relied on the tabletop Maxwell® RSC Instrument to conduct nucleic acid extractions using the Maxwell® Viral TNA Kit. As their testing needs grew, they required more throughput. Dormand worked with Promega Field Support Scientist Rick Grygiel to implement the Maxwell® HT Viral TNA Kit on the Tecan Fluent 780 liquid handler, raising their throughput from 16 to 96 samples per run. When COVID-19 struck, Dormand worked with Rick to quadruple their testing with the addition of another Fluent 780.

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High-Molecular Weight DNA for Long-Read Sequencing

Imagine that you’re putting together a large, complex jigsaw puzzle, comprising thousands of exceptionally small pieces. You lay them all out and attempt to make sense of them. It would be far easier to assemble this puzzle were the pieces larger, containing more of the image advertised on the box. The same can be said when sequencing a genome.

high-molecular weight DNA  Depiction of a DNA helix

Traditional short-read or next-generation sequencing relies on DNA spliced into small fragments (≤300 base pairs) and then amplified. While useful for detecting small genetic variants like single-base changes to the DNA, this type of sequencing can fail to illuminate larger variations (typically over 50 base pairs) in the genome. Long-read sequencing, or third generation sequencing, allows more accurate genome assemblies, facilitating better detection of structural variants like copy number variations, duplications, translocations and inversions that are too large to identify with short-read sequencing. Long-read sequencing has the capability to fill in “dark regions” of a genome that are unfinished and can be used to assemble larger, more complex genomes using longer fragments of DNA, or high-molecular weight (HMW) DNA.

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Linking Evolution to Pregnancy Outcomes: A Study in Gene Expression

Many of the traits characteristic to human pregnancy are unique. In contrast to other mammals, human pregnancy and labor last longer, and humans are more prone to complications, including infertility, preeclampsia and preterm birth. Research recently published in eLife Sciences by Vincent Lynch, PhD, and colleagues explores the history of gene expression in the human uterus, how it differs from other mammals and how changes in expression may be implicated in our susceptibility to disease.

This study is part of the emerging field of evolutionary medicine, where researchers apply modern evolutionary theory to help us understand the mechanisms behind human health and disease. By studying the history of gene expression, researchers and physicians can illuminate the pathways through which evolution has guided the development of modern tissues and organ systems, and how these systems may differ in one species versus the next.

DNA helix. We review a recent publication that explores the history of gene expression in the human uterus
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The Latest Addition to the Lab: A Review of the Spectrum Compact CE System

When it comes to acquiring new equipment, choosing the right instrument for your lab can be daunting―you want to make a worthwhile investment that will go the distance, both in longevity and overall capacity. In a perfect world, the instruments available to you would have been thoroughly tested and reviewed, especially as they compare to one another, making your job that much easier.

In the case of benchtop capillary electrophoresis (CE) instruments, researchers Nastasja Burgardt and Melanie Weissenberger have done just that. Their article, titled “First experiences with the Spectrum Compact CE System”, appeared in the International Journal of Legal Medicine and offered a comprehensive review of the performance of the recently released Spectrum Compact CE System in a forensic genetics laboratory setting.

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Writing Successful Grants: Putting It Into Words

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

After a long and arduous journey, you have finally arrived at the last stage of your quest to create the world’s most inspiring grant proposal: writing it all down.  

One of the most challenging parts of putting together a grant proposal is simply writing it. You must write to build the reviewers’ confidence in you and demonstrate your contributions to your field, effectively illustrating your qualities as a researcher and your capacity to achieve your goals.

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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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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.

For resources including tips on the job search, interviews, conferences and professional development, visit the Professional Skills and Development section of our Student Resource Center.

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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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 “the assay”. 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, “What happens when you treat cells with doxorubicin?”

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 cytotoxicity―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: “Now do you see why I ask for more than one assay?”

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