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Debora Marks

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Debora Marks
Debora Marks
Alma materUniversity of Bristol, University of Manchester, Humboldt University
AwardsOverton Prize, Ben Barres Early Career Award
Scientific career
FieldsArtificial Intelligence, Structural Biology, Bioinformatics
InstitutionsHarvard Medical School
Thesis (2010)
Doctoral advisorReinhard Heinrich, Hanspeter Herzl
Websitehttps://marks.hms.harvard.edu/

Debora S. Marks is a researcher in computational biology and a Professor of Systems Biology at Harvard Medical School.[1] Her research uses computational approaches to address a variety of biological problems.

Career and research

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After an undergraduate degree in medicine she worked in the pharmaceutical industry, coming back to research late in life through a mathematics degree from the University of Manchester.[2] She became interested in microRNAs in the early 2000s[2][3][4] and her work on the biology of microRNAs eventually became a PhD thesis, which she submitted under the guidance of Reinhart Heinrich to Humboldt University of Berlin in 2010.[5] One key contribution was her discovery that transfection of microRNAs into cells counter-intuitively increases the expression of some genes, due to competition for the cellular machinery that processes small RNAs.[6] In collaboration with Alexander van Oudenaarden and Nils Bluthgen, she showed that microRNAs reduce the noise in protein expression when mRNA levels are low, reducing the likelihood of unwanted protein expression as a result of leakage at a gene's promoter.[7]

She is best known for her work on protein structure prediction: her method, which draws on an approach from statistical physics, maximum entropy under constraint, uses correlations between the sequences of protein family members from multiple species to build models of protein structure from sequence alone.[8] In some cases the predicted models are sufficiently accurate to permit molecular replacement of the model into X-ray crystallography data, facilitating phase replacement.[9] The algorithm[10] has been extensively used by other researchers to predict and gain insights into protein structures, for example the structures of the σ2 receptor[11] and the tetraspanin CD81.[12] Marks and her close collaborator Chris Sander have shown that this approach can also be used to predict the structures of non-coding RNAs and RNA-protein complexes,[13] to identify otherwise undetectable structured states in disordered proteins[14] and to predict the functional effects of sequence mutations.[15]

Awards

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In 2016, Marks was awarded the Overton Prize by the International Society for Computational Biology.[16]

In 2018, Marks was awarded the Ben Barres Early Career Award by the Chan Zuckerberg Initiative as part of the Neurodegeneration Challenge Network.[17]

In 2022, Marks was elected as a Fellow of the International Society for Computational Biology.[18]

References

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  1. ^ "Debora S. Marks Lab". Retrieved July 11, 2016.
  2. ^ a b "2016 Overton Prize: Debora Marks". www.iscb.org. Retrieved January 1, 2019.
  3. ^ Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS (2003). "MicroRNA targets in Drosophila". Genome Biology. 5 (1): R1. doi:10.1186/gb-2003-5-1-r1. PMC 395733. PMID 14709173.
  4. ^ John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS (November 2004). "Human MicroRNA targets". PLOS Biology. 2 (11): e363. doi:10.1371/journal.pbio.0020363. PMC 521178. PMID 15502875.
  5. ^ Fogg CN, Kovats DE (July 5, 2016). "2016 ISCB Overton Prize awarded to Debora Marks". F1000Research. 5: 1575. doi:10.12688/f1000research.9158.1. PMC 4934501. PMID 27429747.
  6. ^ Khan AA, Betel D, Miller ML, Sander C, Leslie CS, Marks DS (June 2009). "Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs". Nature Biotechnology. 27 (6): 549–55. doi:10.1038/nbt.1543. PMC 2782465. PMID 19465925.
  7. ^ Schmiedel JM, Klemm SL, Zheng Y, Sahay A, Blüthgen N, Marks DS, van Oudenaarden A (April 2015). "Gene expression. MicroRNA control of protein expression noise". Science. 348 (6230): 128–32. Bibcode:2015Sci...348..128S. doi:10.1126/science.aaa1738. PMID 25838385. S2CID 206633133.
  8. ^ Hopf TA, Colwell LJ, Sheridan R, Rost B, Sander C, Marks DS (June 2012). "Three-dimensional structures of membrane proteins from genomic sequencing". Cell. 149 (7): 1607–21. doi:10.1016/j.cell.2012.04.012. PMC 3641781. PMID 22579045.
  9. ^ Sjodt M, Brock K, Dobihal G, Rohs PD, Green AG, Hopf TA, Meeske AJ, Srisuknimit V, Kahne D, Walker S, Marks DS, Bernhardt TG, Rudner DZ, Kruse AC (April 2018). "Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis". Nature. 556 (7699): 118–121. Bibcode:2018Natur.556..118S. doi:10.1038/nature25985. PMC 6035859. PMID 29590088.
  10. ^ "EVcouplings". evfold.org. Retrieved January 1, 2019.
  11. ^ Alon A, Schmidt HR, Wood MD, Sahn JJ, Martin SF, Kruse AC (July 2017). "2 receptor". Proceedings of the National Academy of Sciences of the United States of America. 114 (27): 7160–7165. doi:10.1073/pnas.1705154114. PMC 5502638. PMID 28559337.
  12. ^ Zimmerman B, Kelly B, McMillan BJ, Seegar TC, Dror RO, Kruse AC, Blacklow SC (November 2016). "Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket". Cell. 167 (4): 1041–1051.e11. doi:10.1016/j.cell.2016.09.056. PMC 5127602. PMID 27881302.
  13. ^ Weinreb C, Riesselman AJ, Ingraham JB, Gross T, Sander C, Marks DS (May 2016). "3D RNA and Functional Interactions from Evolutionary Couplings". Cell. 165 (4): 963–75. doi:10.1016/j.cell.2016.03.030. PMC 5024353. PMID 27087444.
  14. ^ Toth-Petroczy A, Palmedo P, Ingraham J, Hopf TA, Berger B, Sander C, Marks DS (September 2016). "Structured States of Disordered Proteins from Genomic Sequences". Cell. 167 (1): 158–170.e12. doi:10.1016/j.cell.2016.09.010. PMC 5451116. PMID 27662088.
  15. ^ Hopf TA, Ingraham JB, Poelwijk FJ, Schärfe CP, Springer M, Sander C, Marks DS (February 2017). "Mutation effects predicted from sequence co-variation". Nature Biotechnology. 35 (2): 128–135. doi:10.1038/nbt.3769. PMC 5383098. PMID 28092658.
  16. ^ "Feb 17, 2016: ISCB Congratulates 2016 Award Winners, Soren Brunak, Debora Marks, Burkhard Rost, and Serafim Batzoglou". www.iscb.org. Retrieved July 11, 2016.
  17. ^ "Chan Zuckerberg Science Initiative". Neurodegeneration Challenge Network. Archived from the original on December 31, 2019. Retrieved January 1, 2019.
  18. ^ "April 28, 2022: ISCB Congratulates and Introduces the 2022 Class of Fellows!". www.iscb.org. Retrieved June 17, 2022.
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