Research:
Dr. Merrikh performed her graduate studies at Brandeis University, in the laboratory of Dr. Susan Lovett. Her doctoral work focused on DNA damage response pathways in Escherichia coli. She was a NIH postdoctoral fellow in the lab of Dr. Alan Grossman at Massachusetts Institute of Technology. Her postdoctoral work focused on regulation of replication initiation and replication-transcription conflicts in Bacillus subtilis.
The long-term goal of the Merrikh lab is to understand the mechanisms responsible for replication conflicts, their structural and functional consequences, and the mechanism of cellular response. Impediments to the replication machinery, including breaks, DNA binding proteins, and transcription, lead to conflicts that can result in genomic instability, mutagenesis, and a failure to segregate fully replicated genomes. We aim to identify and understand the mechanisms that are essential for avoidance, resolution and toleration of these conflicts. The lab employs molecular, genetic, biochemical, and cell biological approaches in the model system Bacillus subtilis (a Gram-positive bacterium) to understand how cells deal with obstacles encountered by replication. The strategies used by B. subtilis are likely to be conserved in other Gram-positive bacteria, including the harmful pathogens Staphylococcus aureus, Clostridium difficile, Enterococcus faecalis, Listeria monocytogenes, and Streptococcus pneumonia. Furthermore, because replication conflicts occur in all life forms, the basic strategies used to deal with these problems may be conserved across species.
Selected Publications:
Paul S, Million-Weaver S, Cattopadhyay S, Sokurenko E, and Merrikh H. Accelerated gene evolution through replication-transcription conflicts. Nature. In press.
Merrikh H, Zhang Y, Grossman AD and Wang JD. Replication-transcription conflicts in bacteria. Nature Reviews Microbiology. 2012 Jun; 10(7):449-58.
Merrikh H and Grossman AD. Control of the replication initiator DnaA by an anti-cooperativity factor. Mol Microbiol. 2011 Oct;82(2):434-46.
Lilah Rahn-Lee, Merrikh H, Grossman AD and Losick R. The Sporulation Protein SirA Inhibits the Binding of DnaA to the Origin of Replication by Contacting a Patch of Clustered Amino Acids. J Bacteriology. 2011 Mar;193(6):1302-7.
Merrikh H*, Machon C*, Grainger WH, Grossman AD and Soultanas P. Replication-transcription conflicts at rRNA genes lead to replication restart in vivo. Nature. 2011 Feb 24;470(7335):554-7. * Equal contribution.
Smits WK*, Merrikh H*, Bonilla CY and Grossman AD. Association of the helicase loader proteins DnaB and DnaD with targets of the initiator protein DnaA in Bacillus subtilis. J Bacteriology. 2011 Feb;193(3):640-8. * Equal contribution.
Merrikh H, Ferrazzoli AE, Lovett ST. Growth phase and ppGpp control of IraD, a regulator of RpoS stability, in Escherichia coli. J Bacteriology. 2009 Dec;191(24):7x436-46.
Goranov AI, Breier AM, Merrikh H, and Grossman AD. YabA of Bacillus subtilis controls DnaA-mediated replication initiation but not the transcriptional response to replication stress. Mol Microbiol. 2009 Oct;74(2):454-66.
Merrikh H, Ferrazzoli AE, Bougdour A, Olivier-Mason A, Lovett ST. A DNA damage response in Escherichia coli involving the alternative sigma factor, RpoS. Proc Natl Acad Sci USA. 2009 Jan 13;106(2):611-6
