Madhan Tirumalai

Scientific professional prepared for advanced research roles. Extensive experience in designing and conducting experiments, leading to published findings. Known for fostering teamwork and adapting to dynamic research needs, showcasing skills in statistical analysis and grant writing.

• I have 18-20 years of experience in the following overlapping fields: Microbiology, Genomics, Molecular Evolution, Origins of Life, and Astrobiology.
• I have more than 20 publications in peer-reviewed journals, presented several talks/ posters and organized/chaired sessions in International Conferences/Symposia.
• I have actively collaborated with several scientists and academicians on the projects that I have been a part of.
• I have also been an independent reviewer for several journals covering these areas or research.
• I have a track record of supervising/mentoring students from diverse and underrepresented backgrounds, who are often co-authors in publications.
• I actively participate in Education and Public Outreach activities to communicate science to the general public, as well. I believe that my extensive research and mentoring combined with grant writing skills and experience in collaborations make me a strong candidate for this position in your Institute.

• Microbial evolution and genomics
• Directed evolution (of microbes)
• Environmental microbiology
• Bacterial dormancy and mechanisms related to the same
• Mechanisms of microbial resistance to stress, including radiation, antibiotics, and xenobiotics
• Microbiology of human-built environments
• Astrobiology & Origins of Life
• Space Microbiology – microbes of spaceflight and planetary protection concern
• Phage insertion dynamics and genome rearrangement dynamics
• Structure, function and evolution of the molecular machine ribosome, and nucleic acid RNA
• Bottom-up prebiotic chemistry – exploring RNA sequence space using dynamic combinatorial chemistry

• EAGER - Exploring the RNA World and the RNA-peptide world hypothesis using a novel Dynamic Combinatorial Chemistry (DCC) system, Madhan R Tirumalai, George E. Fox, National Science Foundation, NSF-MCB-EAGER 2227347, 08/01/22, 07/31/25, 6 months, 12 months
• NSF 22-606 Pathways to Increasing Complexity in an RNA World With and Without Peptides, Madhan Tirumalai, George Fox, NSF, 04/01/25, 03/31/28, 12/01/24
• NIH-R21 Characterization of the mycobactericidal (microbicidal) activity of lysates of an actinobacterium T. phoenicis, Madhan Tirumalai, William Widger, Abhishek Mishra, National Institute of Health, 12/01/25, 11/03/27, 02/01/25

Papers submitted:

• Tirumalai MR, Ali S, Widger W, Fox GE (2025). Tersicoccus phoenicis (Actinobacteria), a spacecraft assembly isolate, exhibits dormancy, mBio.

Peer-Reviewed Publications 

• Tirumalai MR (2024). “Education and public outreach: communicating science through storytelling”, Journal of Microbiology & Biology Education 0: Apr 25; 25(1):e00209-23, doi:10.1128/jmbe.00209-23. (PMID: 38661406; PMCID: PMC11044642).
• Tirumalai MR, Sivaraman RV, Kutty LA, Song EL, Fox GE (2023). "Ribosomal Protein Cluster Organization in Asgard Archaea", Archaea, vol. 2023, Sep 29;2023:5512414. doi: 10.1155/2023/5512414. (PMID: 38314098; PMCID: PMC10833476).
• Tirumalai MR, Anane-Bediakoh D, Rajesh S, Fox GE (2021). “Net charges of the ribosomal proteins of the S10 and spc clusters of halophiles are inversely related to the degree of halotolerance”, Microb Spectr. 9(3):e0178221. https://doi.org/10.1128/spectrum.01782-21. (PMID:34908470; PMCID:PMC8672879).
• Tirumalai MR, Tran Q, Paci M, Chavan D, Marathe A and Fox GE (2018). “Exploration of an RNA Sequence Space in the Absence of a Replicase.” J Mol Evol (2018).June:86(5):264-276. https://doi.org/10.1007/s00239-018-9846-8. Epub 2018 May 11.(PMID:29748740).
• Tirumalai MR, Stepanov VG, Wünsche A, Montazari S, Gonzalez RO, Venkateswaran K, Fox GE (2018). “B. safensis FO-36bTand B. pumilus SAFR-032: A Whole Genome Comparison of two Spacecraft Assembly Facility Isolates.” BMC Microbiol (2018). Jun 8;18(1):57. https://doi.org/10.1186/s12866-018-1191-y. (PMID:29884123, PMCID:PMC5994023).
• Stepanov VG, Tirumalai MR, Montazari S, Checinska A, Venkateswaran K, Fox GE (2016)."Bacillus pumilus SAFR-032 Genome Revisited: Sequence Update and Re Annotation", PLoS One. 2016 Jun 28; 11(6):e0157331. https://doi.org/10.1371/journal.pone.0157331. (PMID: 27351589, PMCID:PMC4924849).
• Tirumalai MR, Rastogi R, Zamani N, O’Bryant Williams E, Allen S, Diouf F, Kwende S, Weinstock GM, Venkateswaran KJ, Fox GE (2013). “Candidate Genes That May Be Responsible for the Unusual Resistances Exhibited by Bacillus pumilus SAFR-032 Spores”, PLoS One, Jun 14; 8(6):e66012. (PMID: 23799069, PMCID: PMC3682946), DOI:10.1371/journal.pone.0066012.
• Tirumalai MR, Fox GE (2013). “An ICEBs1-like element may be associated with the extreme radiation and desiccation resistance of Bacillus pumilus SAFR-032 spores”, Extremophiles, Sep; 17(5):767-74. (PMID: 23812891), DOI: 10.1007/s00792-013-0559-z,Epub 2013 Jun 28.
• Gioia J, Yerrapragada S, Qin X, Jiang H, Igboeli OC, Muzny D, Dugan-Rocha S, Ding Y, Hawes A, Liu W, Perez L, Kovar C, Dinh H, Lee S, Nazarath L, Blyth P, Holder M, Buhay C, Tirumalai MR, Liu Y, Dasgupta I, Bokhetache L, Fujita M, Karouia F, Moorthy PE, Siefert J, Uzman A, Buzumbo P, Verma A, Zwiya H, McWilliams BD, Olowu A, Clinkenbeard KD, Newcombe D, Golebiewski L, Petrosino JF, Highlander SK, Nicholson WL, Fox GE, Venkateswaran K & Weinstock GM (2007), "Paradoxical DNA Repair and Peroxide Resistance Gene Conservation in Bacillus pumilus SAFR-032", PLoS ONE 2(9): e928. (PMID: 17895969, PMCID: PMC1976550), DOI: 10.1371/journal.pone.0000928.
• Highlander, SK, Hulten KG, Qin X, Jiang H, Yerrapragada Y, Mason EO Jr, Shang Y, Williams T, Fortunov RM, Liu Y, Igboeli O, Petrosino J, Tirumalai MR, Uzman A, Fox G, Cardenas AM, Muzny D, Hemphill L, Ding Y, Dugan S, Blyth PR, Buhay CJ, Dinh HH, Hawes ACF, Holder MK, Kovar CL, Lee SL, Liu W, Nazareth LV, Wang Q, Zhou J, Kaplan SL, & Weinstock GM (2007), "Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus", BMC Microbiol 7(1):99. (PMID: 17986343, PMCID: PMC2222628), DOI: 10.1186/1471-2180-7-99.
• Petrosino JF, Xiang Q, Karpathy SE, Jiang H, Yerrapragada S, Liu Y, Gioia J, Hemphill L, Gonzalez A, Raghavan TM, Uzman A, Fox GE, Highlander S, Reichard M, Morton RJ, Clinkenbeard KD, & Weinstock GM (2006). “Chromosome rearrangement and diversification of Francisella tularensis revealed by the type B (OSU18) genome sequence”, J Bacteriol. 188(19):6977-85. (PMID: 16980500, PMCID: PMC1595524), DOI: 10.1128/JB.00506-06. (Raghavan TM refers to Madhan R Tirumalai).
• Mishra GR, Suresh M, Kumaran K, Kannabiran N, Suresh S, Bala P, Shivakumar K, Anuradha N, Reddy R, Raghavan TM, Menon S, Hanumanthu G, Gupta M, Upendran S, Gupta S, Mahesh M, Jacob B, Mathew P, Chatterjee P, Arun KS, Sharma S, Chandrika KN, Deshpande N, Palvankar K, Raghavnath R, Krishnakanth R, Karathia H, Rekha B, Nayak R, Vishnupriya G, Mohan Kumar HG, Nagini M, Sameer Kumar GS, Jose R, Deepthi P, Mohan SS, Gandhi TKB, Harsha HC, Deshpande KS, Sarker M, Prasad TSK, & Pandey

A. “Human protein reference database - 2006 update”, Nucleic Acids Res Jan 1;34(Database issue):D411-4. (PMID: 16381900, PMCID: PMC1347503), DOI:

10.1093/nar/gkj141. (Raghavan TM refers to Madhan R Tirumalai).

Tirumalai MR, Rivas M,Tran Q,Fox GE (2021). “The Peptidyl Transferase Center: a Window to the Past”, Microbiol Mol Biol Rev. Nov 10;85(4):e0010421. https://doi.org/10.1128/MMBR.00104-21. (PMID:34756086; PMCID:PMC8579967).

Tirumalai MR, Kaelber JT, Park DR, Tran Q, Fox GE (2020). “Cryo-electron microscopy visualization of a large insertion in the 5S ribosomal RNA of the extremely halophilic archaeon Halococcus morrhuae”, FEBS Open Bio 10:1938-1946, https://doi.org/10.1002/2211-5463.12962. (PMID:32865340, PMCID:PMC7530397).

This is the first cryo-electron microscopy (cryo-EM) map of the ribosome from a member of the Halococcus archaea. The high concentrations of salt needed for the growth of H. morrhuae as well as the ribosome stability posed challenges. High amounts of salt in cell suspensions severely interfere with the contrast between structures of molecules (proteins, RNA, DNA) or cells and the surrounding medium in cryo-EM. At the salt concentrations (close to the saturation limit),

required for the Halococcus ribosome stability, salt can quickly crystallize. This influenced the quality of the sample solution that is placed on the grids used for cryo-EM, and created challenges in both sample preparation and imaging. This was overcome by growing cells in very large quantities and obtaining a larger dataset of ribosome particles in samples, moving from an initial 15,000 particles to over 100,000 particles. This increased dataset helped improve magnification and resolution of the results.

Camprubí E, de Leeuw JW, House CH, Raulin F, Russell MJ, Spang A, Tirumalai MR, Westall F (2019). ‘The Emergence of Life’. Space Science Reviews, 215 (8), https://doi.org/10.1007/s11214-019-0624-8. (My specific contribution to this review is Section 3 “The RNA World: Reality or Dogma?”)

This publication is now included as a book chapter, Camprubí E, et al. 2021. "Emergence of Life". In “Ocean Worlds: Habitability in the Outer Solar System and Beyond”, (ed. A Coustenis, Rodrigo, R., Spohn, T., Hand, K.P., Hayes, A., Olsson-Francis, K., Postberg, F., Sotin, C., Tobie, G., Raulin, F., Walter, N., L’Haridon, J), pp. 29-82, Space Sciences Series of ISSI (International Space Science Institute), Series Volume 77 (2021), Springer Netherlands (Hardcover ISBN 978-94-024-2069-

2) https://www.springer.com/us/book/9789402420692(http://www.issibern.ch/publication s). This is a collection of in-depth papers informed by the contributions and discussions at the workshop "ExoOceans: Space Exploration of the Outer Solar System Icy Moons Oceans International Space Science Institute" 18-22 June 2018.

Tirumalai MR, Karouia F, Tran Q, Stepanov VG, Bruce RJ, Ott CM, Pierson DL, Fox

GE (2019). “Evaluation of Acquired Antibiotic Resistance in Escherichia coli exposed to long-term Low Shear Modelled Microgravity and Background Antibiotic Exposure”, mBio(2019),https://doi.org/10.1128/mBio.02637-18. (PMID:30647159,PMCID:PMC6336426).

Tirumalai MR, Karouia F, Tran Q, Stepanov V, Bruce RJ, Ott MC, Pierson DL, Fox GE (2017). “The Adaptation of E. coli Cells Grown in Simulated Microgravity for an Extended Period is Both Phenotypic and Genomic”, npj Microgravity, volume 3, Article number: 15, http://dx.doi.org/10.1038/s41526-017-0020-1 (PMID: 28649637, PMCID: PMC5460176).

Tirumalai MR, Fox GE (2019). ‘Reply to Mortazavi, "Acquired Antibiotic Resistance in Escherichia coli Exposed to Simulated Microgravity: Possible Role of Other Space Stressors and Adaptive Responses"’. mBio(2019), 10(2), e00391-19, https://doi.org/10.1128/mBio.00391-19.(PMID:30914512, PMCID:PMC6437056).

Raghavan TM, Furtado I (2005), “Expression of carotenoid pigments of haloarchaeal cultures exposed to aniline.” Environ Toxicol. Apr; 20(2):165-9. PMID: 15793825, DOI:10.1002/tox.20091. (Raghavan TM refers to Madhan R Tirumalai).

Raghavan TM, Furtado I (2004), “Occurrence of halophilic archaea in continental shelf sediments off the West Coast of India”, Current Science, Vol.86, and No.8:1065-1067.

During March-April, 1998, April, 1999, and April, 2001, I worked as a research analyst/chemist working offshore aboard the research vessel Sagar Paschimi (owned by the Department of Ocean

Development, India) commissioned by the Institute for Petroleum Safety and Environment Management, ONGC (Oil and Natural Gas Commission, Govt. of India), Betul, Goa, India.

My work aboard involved chemical analysis - viz., nitrite, nitrate, phosphate and silicate analysis of the seawaters at different depths at various spots around the ONGC offshore oil rig installations; and

Raghavan TM, Furtado I (2000), “Tolerance of an Estuarine Halophilic Archaebacterium to

Crude Oil & Constituent Hydrocarbons”, Bull. Environ. Contam. Toxicol. Springer Verlag, 65(6): 725 –731. PMID: 11080352.

Shaila Yerrapragada, Animesh Shukla, Kymberlie Hallsworth-Pepin, Kwangmin Choi, Aye Wollam, Sandra Clifton, Xiang Qin, Donna Muzny, Sriram Raghuraman, Haleh Ashkib, Akif Uzman, Sarah Highlander, Bart Fryszczyna, Brendon Bingwa, Catherine (Horton) Schaffer, George Fox, Madhan R Tirumalai, Yamei Liu, Sun Kim, David M. Kehoe, George Weinstock (2015). “Extreme Sensory Complexity Encoded in the 10 Mb Draft Genome Sequence of the Chromatically Acclimating Cyanobacterium Tolypothrix sp. PCC 7601”, Genome Announcements. 2015 May 7; 3(3).pii:e00355-15. (PMID: 25953173, PMCID: PMC4424289), DOI: 10.1128/genomeA.00355-15.

Laurie E. Calvet, Madhan R. Tirumalai, Quyen Tran, George E. Fox. “Understanding Ribosomal Structural Differences Between Bacteria and Archaea Using Network Graphs”. 2022 May. DOI: 10.1002/essoar.10511478.1.

· A review paper on “Biofilms” with the GeneLab Biofilms Subgroup (under the Microbes Analysis Working Group(AWG)), with me as a co-author is under preparation. My contribution pertains to biofilms, fitness costs and antibiotic resistance under simulated microgravity and space conditions.

· One paper with collaborator Dr. Fabia Ursula Battistuzzi (Oakland University, MI, USA) is under preparation. This paper will present results of sequencing non-pathogenic E. coli MG1655 that has been exposed to simulated microgravity with and without trace antibiotic exposure. The sequences obtained using short-read and long-read (PacBio) technologies will be the focus of the paper.

· Connectivity in the Bacterial Ribosome. Calvet LE, Nahmias B, Tran Q, Fox GE, Tirumalai MR (2024).

· Novel insertions in the 23S ribosomal RNA of members of bacterial candidate phyla radiation, Tirumalai MR, Petrov A, Williams LA, Fox GE.

· I have made a minor contribution to the book “Never Home Alone” by Dr. Robb Dunn (North Carolina State University, Raleigh, NC) (http://robdunnlab.com/people/rob-dunn/) that is centered on ‘microscopic and microbial life in enclosed human habitats, including homes’. My contribution is related to microbial diversity on the International Space Station and Spacecraft Clean Room facilities.

• An Assay to measure Resuscitation in Actinobacteria, S. Ali, M.R. Tirumalai, G. E. Fox, W. Widger, 03/27/25, ASM Texas Branch Spring 2025 Meeting, Mt. Lebanon Camp, Cedar Hill, TX
• Planetary Protection Metagenomics in Spaceflight, 11/19/24, NASA Ames, Mountain View, CA

• Research Assistant Professor, Biology & Biochemistry, University of Houston, 06/01/20, Present
• Post-Doc, Biology & Biochemistry, University of Houston, 04/01/06, 05/31/20
• Research Scientist, Institute of Bioinformatics, Bengaluru, India, 06/01/04, 11/30/05

• University of Houston

• 2024, September 30-December 1: Antimicrobial Databases and Genotype Prediction: Data Sharing and Analysis, FutureLearn online platform, Wellcome Connecting Science Courses, Wellcome Genome Campus, UK.

• 2017, July 10-14: UCLA Computational Genomics Summer Institute Short Program CGSI Short Course, University of California, Los Angeles. (http://computationalgenomics. bioinformatics.ucla.edu/short-program-2/).

• 2014:

o June 19-20: Software School on New Methods for Phylogenomics and Metagenomics, Co-located with Evolution 2014 Raleigh Convention Center, NC.

o May 31: PhyloLab Conference on Computational Biology, the University of Texas at Austin.

• 2012:

o September 5-7: 9th International Workshop on Complex Systems and Networks (IWCSN) held at the Institute of Mathematics & its Applications (IMA), University of Minnesota, Minneapolis, USA.

o August 24-26: 4th Annual Astrobiology Research Focus Group (RFG) Workshop, Catalina Island, CA, (http://astrobiology.com/2012/10/2012-early-career- research-focus-group.html).

• 2011, June 2-4: 3rd Annual Astrobiology RFG Workshop, Montana, USA.

• 2010, July 25 – August 6: Annual Workshop on Molecular Evolution, Marine Biological Laboratory (MBL), Woods Hole, Massachusetts. This is the most prestigious workshop serving the field of evolutionary studies.

• 2009, June 22-26: NAI-CAB International Summer School of Astrobiology "Josep Comas i Solà" on Earth's Extremophiles and the Habitability of Extraterrestrial Environments”, held at the summer campus of the Spanish National University, UIMP, Santander, Spain.

• 2007, October 29th – November 2nd: Annual Program Year Workshop “RNA in Biology, Bioengineering and Nanotechnology”, IMA, University of Minnesota, Minneapolis, USA.

• 2006, August 20 – September 1: Theoretical Course of the Baltic Summer School “Stem Cell Biology: Future perspectives & possible treatment options” organized by the Christian-Albrechts University of Kiel, Germany, and the Universities of Copenhagen & Lund.

• 2003, November 3-5: "IV Workshop on Advances in Molecular Medicine" BBVA Foundation, Madrid, Spain.

• 2001, July 23-26: Workshop “Extremophiles research : Theory and Techniques”, Center of Marine Biotechnology, Columbus Center, University of Maryland Biotechnology Institute, Baltimore, USA- awarded 2.2 Continuing Education Units (CEU) for the same.

• Awarded a grant by the National Science Foundation:

Title: EAGER - Exploring the RNA World and the RNA-peptide world hypothesis using a novel Dynamic Combinatorial Chemistry (DCC) system

PI: Madhan R Tirumalai, Co PI: George E. Fox

Sponsor: National Science Foundation (Award No. NSF-MCB-EAGER 2227347) Performance Period: 08/01/2022 – 07/31/2025 (No Cost Extension valid until 07/31/2025) Annual Effort: 6 months (2022-2023), 12 months (2023-2024)

This project utilizes a novel dynamic combinatorial chemistry (DCC) approach to how RNA sequence space could have been explored in an RNA World in the absence of a replicase, and whether this process is enhanced by peptides or AAs. The system also addresses the practical constraints of studying the effect of very long-term changes on laboratory time scales.

This project involves a combination of biochemistry (calibration of the enzymes used in the DCC system), sequencing and analysis of the sequences (molecular biology and bioinformatics).

• NASA's Planetary Biology Internship (NASA-PBI) (http://www.mbl.edu/education/courses/other_programs/ pbi.html) to work with Prof. George E. Fox, Dept of Biology and Biochemistry, the University of Houston, USA.

• Qualified the CSIR-UGC (University Grants Commission) National Eligibility Test - mandatory for anyone to either pursue research or to be a lecturer in India.

• Awards and Scholarships during PhD Years

I was awarded various scholarships, to present my work at international conferences, and workshops, by several international institutions, foundations, and organizations as follows:

· The National University of Singapore (2001),

· George Mason University's Institute for Bioscience, Bioinformatics and Biotechnology (2001),

· the National Institute of Environmental Health Sciences (NIEHS) Superfund Basic Research Program (2002),

· the United States Environmental Protection Agency (USEPA) (2002),

· the United States Department of Energy (DOE)(2002),

· the United States Food & Drug Administration (USFDA) (2002),

· Heinrich Böll Stiftung (Germany) (2002),

· Nature Publications (2003),

· the American Chemical Society (2003), and

· the BBVA Foundation (Madrid, Spain) (2003).