Cell Cycle and Epigenetics Research: The Bee’s Knees of Genetics

So Who Works in the Lab?

Dr. James of course!

Dr. James of course!

Andrew Sydenstricker

Andrew Sydenstricker




I’m Andrew Sydenstricker, a rising sophomore. I’m looking to either attend graduate or medical school after my four years here at Gettysburg College, with a possible two year gap serving the Peace Corps. Majoring in BMB, I’m very interested in all of the sciences, but my passion is in Biology. Working in Dr. James’s Lab has been an amazing experience, and I am very fortunate to work under such a great person and mentor.






Matthew Dunworth

Matthew Dunworth




Hi! My name is Matt Dunworth and I am a rising junior and BMB major!  I work in Dr. James lab which is perfect for my love of genetics and all things DNA.  I plan to do something oncology related with my future, once I become a Gettysburg College graduate in 2016!  So far I have had a blast working in the lab this summer, and have learned a lot even through frustrating times.  I’m excited to continue to do research this summer and keep on going for the next two years!






Now about the Research…


Cell Cycle Background 

In Dr. James’ lab, we conduct cell cycle research in Aspergillus nidulans, our favorite model organism.  The cell cycle simply refers to the normal cycle of growth and reproduction by which one cell divides itself out of existence to form two identical daughter cells.  This process, called mitosis, is fundamentally risky and complex, because in order to complete it successfully, the cell must break down and reorganize many components.  For example, the protective membrane surrounding the nucleus dissolves and the chromosomes contained therein are compressed and compacted by a factor of 10-100 fold. The microtubules that form the cell cytoskeleton are broken apart and reassembled into spindle apparatus.  The spindle apparatus then moves into the nucleus, captures the chromosomes, and pulls them apart to form two new nuclei that contain the same genetic information as one another and the mother cell that formed them.

The cell cycle is a tightly controlled process.  Regulation of the cell cycle depends upon a group of proteins that are highly conserved across all eukaryotes, making Aspergillus nidulans (a filamentous fungus and a great example of a eukaryote!) an excellent model organism for cell cycle research due to its ease of use and short life cycle.  One such protein is encoded by the nimX gene.  The nimX gene codes for the CDK1 protein, which in conjunction with nimECYCLINB, forms the CDK1/CYCLINB protein kinase, a complex of two proteins that governs the transition of a cell from its normal mode of growth into mitosis.  Since nimX activity is absolutely required for entry into mitosis, mutations in the nimX gene prevent a cell from entering mitosis (hence the name of nimX never in mitosis).  These nimX mutations block the cell cycle at high temperature, causing the cell to expire, but at lower temperatures, the nimX gene remains functional, allowing normal growth.


All about snxA, our cell cycle gene of choice

In particular, we are working on a gene called snxA, which has been identified as a suppressor of the nimX gene (this is also where snxA gets its name: suppressor of nimX).  Two mutations in the snxA gene were  identified, snxA1 and snxA2, by virtue of their ability to alleviate, or suppress, the heat sensitivity of nimX2CDK1, thereby allowing mitosis to occur as usual.  Therefore, the two snxA mutations rescue the mitotic defect of the nimX2 mutation, forming quite an interesting relationship.  It is as if, when snxA is mutated, the nimXCDK1 gene is no longer needed for mitosis.  After realizing this a few years ago, the James laboratory embarked on a journey to identify the snxA gene and map the snxA1 and snxA2 mutations, with a mission in mind to pin down exactly what changes in the DNA of the snxA gene caused the pair of mutations.  To our great surprise (and frustration!), after many rounds of sequencing, no change in the mutant DNA sequences were found, leading us to speculate that forces beyond DNA might be at work in the snxA mutants.  Such forces, acting above and beyond the level of DNA, and determining whether a given gene is turned on (activated) or off (repressed), collectively fall under the term ‘epigenetics’.


Epigenetics: Some background and our area of research

So what is epigenetics, you ask?  Simply defined, epigenetics is the regulation of gene expression controlled by a type of chemical modification to the DNA (DNA methylation) and several types of modifications (acetylation and methylation) to the proteins that associate with DNA in chromosomes (the complex architecture of DNA + protein that makes up a chromosome is called ‘chromatin’).  In Aspergillus nidulans, however, the only source of epigenetic variance stems from the acetylation and methylation of the various histone proteins that comprise majority of proteins found in chromatin.  Through the strategic positioning of acetyl and methyl groups on these histones, genes can be more actively transcribed, as the addition of these groups negates the positive charge of amino acids in the histones, pushing the negatively charged DNA away from the chromatin.  This process ‘opens’ up the DNA, allowing more active transcription of the genes by the cellular machinery.  After finding no nucleotide changes in the snxA mutant sequences, we now believe that a stable epigenetic mutation may be at work in the snxA mutants.  In this case, a stable mutation can be passed on from generation to generation through the various chromatin modifications that may occur (no one yet understands how the cell retains this chromatin modification memory and is able to consistently replicate it in succeeding generations).  What I (Matt) am working on is trying to prove that there is in fact some epigenetic funny business going on at the snxA locus.  I am doing this by PCR amplifying different fragments of the snxA sequence from snxA1 and snxA2 mutants, after which I will transform these mutant-derived DNAs back into snxA1 and snxA2 mutants.  The thought behind this is that if the gene is in fact being controlled by an epigenetic alteration, then the process of PCR will provide naked strands of DNA lacking histone proteins and their associated modifications.  Without these chromatin marks, there will be no epigenetic memory, and by transforming the naked mutant-derived snxA DNA fragments back into snxA mutants, we hope to  restore the snxA gene to a wild-type state.  Now that is a lot easier said than done, and so I am currently working on trying to obtain the last piece of the gene that we wish to transform, a piece that spans almost the entirety of the snxA region (this region has been unusually difficult to isolate using PCR, reinforcing the thought that there is something weird going on in this stretch of DNA).  After we gather this last fragment of DNA, we will be ready for some transformations and should then be one step closer to an answer!  An exciting time in the lab and world that is cell cycle research!

So now that you have read (probably skimmed…) this, you should be caught up on all that is snxA! Thanks for reading and check back in the upcoming weeks for a follow up!



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