Center on the Biology of Aging

Graduated: 2018
Current Location: Brown University, Providence, RI 

Mentor: David M. Rand

Description of trainee's research project and progress: John is a URM student who matriculated in the MCB Program in September 2012, and began his research in Dr. Rand's lab in June 2013. He was appointed to the MBoA T32 in his third year, September 2014, after being supported by the IMSD Program for two years. He is being terminated from the MBoA Program slightly ahead of schedule, on June 1, 2016, because he is transitioning to his F31 award (see below). He is currently completing his fourth year in the MCB Program. His project examines the reciprocal molecular signals that are generated by interactions between nuclear and mitochondrial genomes. This work exploits Drosophila lines, referred to as introgression lines, with a common isogenic nuclear genome but mitochondrial genomes of two separate species (such as melanogaster and simulans). John's project focuses on TOR signaling in these lines. By looking at functional capacity of isolated mitochondria and specific ETC complexes in response to TOR inhibitors he found several novel cases of mito-nuclear cooperation. Most interestingly, inhibition of TOR with rapamycin regulated mitochondrial capacity differently in males than in females. In particular, the effects in isogenic lines possessing a coevolved mtDNA were not seen in the lines with foreign mitochondria, indicating a sex-dependent role for mito-nuclear cooperation. Surprisingly, more recent experiments showed that using RNAi to reduce TOR-complex formation alters mitochondrial capacity similarly in both sexes and all lines. This was unexpected as both rapamycin and RNAi are reducing TOR-kinase activity, but supports a model in which signals generated by the inactive TOR complex are having sex-dependent effects. John is currently in the process of elaborating these results in preparation for a paper. He has also begun generating a large RNA-seq data set to analyze the rapamycin response in these lines.

Conference presentations:
1) Santiago JC, Hale-Philips C, Rand DM. Sexual asymmetry in Drosophila TOR signaling. SACNAS National Conference, Washington, DC, October 29-31, 2015, (Abstract-talk).

2)John C. Santiago, Cynthia A. Hale-Phillips, Brian M. Franklin, Trung V. Ho, David M. Rand. Gender inequality for mitochondrial function in response to TOR inhibition with rapamycin and RNAi in Drosophila. The PI3K-mTOR-PTEN Network in Health & Disease Conference, Cold Spring Harbor Laboratory, NY, August 30-September 3 2016 (Poster)

3) John C. Santiago, Cynthia A. Hale-Phillips, Brian M. Franklin, Trung V. Ho, David M. Rand. Gender inequality for mitochondrial function in response to TOR inhibition with rapamycin and RNAi in Drosophila. SACNAS National Conference, Long Beach, CA, October 12-16, 2016 (Talk)

4) John C. Santiago, Cynthia A. Hale-Phillips, Brian M. Franklin, David M. Rand. mtDNA Genotype Alters the Transcriptional Response to Rapamycin. The 58th Annual Drosophila Research Conference, San Diego CA, March 29 – April 7 2017 (Poster)

5) John C. Santiago, Cynthia A. Hale-Philips, David M. Rand. Mitochondrial Genotype Alters Metabolic and Transcriptional Regulation by TOR Signaling in Drosophila. Molecular Biology of Aging Symposium. Brown University November 4 2017 (talk)

Fellowships and other support: F31 GM117851, "Mitochondrial genes and TOR signaling in Drosophila", start date 6/1/2015.

Honors:
1) Annual ABRCMS Conference, San Antonio, TX, Nov 12-15, 2014, attended as the student representative of the MCB Graduate Program
2) Featured in the IMSD View newsletter, Vol. 7, issue 2, page 3 (Appendix-24)
3) Annual SACNAS National Conference MCB student representative 2015 in Washington DC and 2016 in Long Beach CA
4) Awarded “Best Graduate Student Oral Presentation in Biomedical Research” at the 2016 SACNAS National Conference