Rosbash's research group cloned the Drosophila period gene in 1984 and proposed the Transcription Translation Negative Feedback Loop[2] for circadian clocks in 1990.

Along with Michael W. Young and Jeffrey C. Hall, he was awarded the 2017 Nobel Prize in Physiology or Medicine "for their discoveries of molecular mechanisms controlling the circadian rhythm".

After arriving at Brandeis, Rosbash collaborated with co-worker Jeffrey Hall[7] and investigated the genetic influences on circadian rhythms of the internal biological clock.

In May 1998, Rosbash et al. found a homolog for mammalian Clock that performed the same function of activating the transcription of per and tim that they proceeded to call dClock.

[10] In November 1998, Rosbash et al. discovered the cryb Drosophila mutant, which led to the conclusion that cryptochrome protein is involved in circadian photoreception.

These mutations cause the peak of the evening activity to occur earlier and later, respectively, compared to wildtype per+ flies.

This was supported by the evidence that per precursor RNA cycles with the same phase as mature transcripts, and oscillate with respect to Zeitgeber Time (ZT).

[13] The Akhilesh Reddy group has shown, using a range of unbiased -omics techniques (RNA-sequencing, proteomics, metabolomics) that Drosophila S2 cells display circadian molecular rhythms.

[17][16] These findings substantiate the work above in demonstrating the TTFL model of the fly clockwork cannot explain the generation of circadian rhythms.

Homozygous cycle0 mutants are arrhythmic in locomotor activity and heterozygous cycle0/+ flies have robust rhythms with an altered period of rhythmicity.

[10] In 1998, Rosbash et al. discovered a Drosophila mutant exhibiting flat, non-oscillating levels of per and tim mRNA, due to a null mutation in the cryptochrome gene.

The failure of cryb mutants to synchronize to light dark cycles indicates that cryptochrome’s normal function involves circadian photoreception.

LNV neurons express PDF (pigment dispersion factor), which was initially hypothesized to be a clock output signal.

Mutants for the pdf neuropeptide gene (pdf01) as well as flies selectively ablated for LNV produced similar behavioral responses.

However, the mRNAs appear to be expressed in a circadian and neuron-specific manner, for which his lab has taken interest in determining whether this provides a link to the distinct functions of certain neuronal groups.

[19] Today, Rosbash continues to research mRNA processing and the genetic mechanisms underlying circadian rhythms.