Ciliopathies and how let-7 contributes

My lab’s primary research interests are in pediatric disorders, especially those that occur when cilia are defective or not properly developed. The result of such defects are known as ciliopathies—genetic disorders of cellular cilia. Additionally, the lab has been working to developing assays for the known portions of the morbid pediatric genome and variants present in the genes of the patients that they work with. Through the Neonatal and Perinatal Research Institute, The Center for Human Disease Modeling works with several science departments and clinics to study and understand the results of their experiments in order to aid physicians in treating patients—especially young children and infants who have physical abnormalities that have no obvious cause.

My mentor has given me a project that continues off of a previous undergraduate’s research involving a micro-RNA known as let-7. The goal of this person’s research was to determine how different levels of let-7 inhibit or supplement the growth of functional cilia within a cell. The findings were that elevated levels of let-7 facilitated ciliogenesis, while suppressing let-7 caused defects in ciliogenesis.

It is understood that let-7 is an mRNA expression inhibitor, and that this inhibiting of mRNAs plays a key role in the success or failure of ciliogenesis. Along with my secondary mentor, I am to aid in furthering the aforementioned research by helping to understand which mRNAs let-7 targets.

The idea is that if miRNA (micro RNA) inhibitors are present, let-7 will then be repressed, and the mRNA targets of let-7 will therefore be expressed. The expression of these mRNAs will cause defects in ciliogenesis. Thus, if we were to elevate the levels of some mRNA suspects (of which, there are around thirty), we would look to see if these elevated levels would cause defects of ciliogenesis.

So far, I’ve just been learning the ropes, and the necessary reactions needed to prepare plasmids containing the genetic information that we’re looking for and express them in cells for further experimentation. I’m not entirely sure yet what that further experimentation is, but even the things that I’m learning how to do—the mere basics of growing E. coli, purifying DNA, sequencing DNA, transforming cells, and even learning how to use the equipment—is nonetheless invaluable to me, and I’m excited to learn more. We’re hopefully almost finished with the sequencing of the DNA (and I might be learning mutagenesis if any of the plasmid inserts have mutations), and once that happens, my secondary mentor tells me she might “graduate me” to the cellular level.

Whatever that means!

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