Debora Marks Explained

Debora Marks
Fields:Artificial Intelligence, Structural Biology, Bioinformatics
Workplaces:Harvard Medical School
Alma Mater:University of Bristol, University of Manchester, Humboldt University
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Thesis Year:2010
Doctoral Advisor:Reinhard Heinrich, Hanspeter Herzl
Awards:Overton Prize, Ben Barres Early Career Award
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Website:https://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

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[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

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]

External links

Notes and References

  1. Web site: Debora S. Marks Lab. July 11, 2016.
  2. Web site: 2016 Overton Prize: Debora Marks. www.iscb.org. 2019-01-01.
  3. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS . MicroRNA targets in Drosophila . Genome Biology . 5 . 1 . R1 . 2003 . 14709173 . 395733 . 10.1186/gb-2003-5-1-r1 . free .
  4. John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS . Human MicroRNA targets . PLOS Biology . 2 . 11 . e363 . November 2004 . 15502875 . 521178 . 10.1371/journal.pbio.0020363 . free .
  5. Fogg CN, Kovats DE . 2016 ISCB Overton Prize awarded to Debora Marks . F1000Research . 5 . 1575 . July 5, 2016 . 27429747 . 4934501 . 10.12688/f1000research.9158.1 . free .
  6. Khan AA, Betel D, Miller ML, Sander C, Leslie CS, Marks DS . Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs . Nature Biotechnology . 27 . 6 . 549–55 . June 2009 . 19465925 . 2782465 . 10.1038/nbt.1543 .
  7. Schmiedel JM, Klemm SL, Zheng Y, Sahay A, Blüthgen N, Marks DS, van Oudenaarden A . Gene expression. MicroRNA control of protein expression noise . Science . 348 . 6230 . 128–32 . April 2015 . 25838385 . 10.1126/science.aaa1738 . 2015Sci...348..128S . 206633133 .
  8. Hopf TA, Colwell LJ, Sheridan R, Rost B, Sander C, Marks DS . Three-dimensional structures of membrane proteins from genomic sequencing . Cell . 149 . 7 . 1607–21 . June 2012 . 22579045 . 3641781 . 10.1016/j.cell.2012.04.012 .
  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 . Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis . Nature . 556 . 7699 . 118–121 . April 2018 . 29590088 . 6035859 . 10.1038/nature25985 . 2018Natur.556..118S .
  10. Web site: EVcouplings. evfold.org. 2019-01-01.
  11. Alon A, Schmidt HR, Wood MD, Sahn JJ, Martin SF, Kruse AC . 2 receptor . Proceedings of the National Academy of Sciences of the United States of America . 114 . 27 . 7160–7165 . July 2017 . 28559337 . 5502638 . 10.1073/pnas.1705154114 . free .
  12. Zimmerman B, Kelly B, McMillan BJ, Seegar TC, Dror RO, Kruse AC, Blacklow SC . Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket . Cell . 167 . 4 . 1041–1051.e11 . November 2016 . 27881302 . 5127602 . 10.1016/j.cell.2016.09.056 .
  13. Weinreb C, Riesselman AJ, Ingraham JB, Gross T, Sander C, Marks DS . 3D RNA and Functional Interactions from Evolutionary Couplings . Cell . 165 . 4 . 963–75 . May 2016 . 27087444 . 5024353 . 10.1016/j.cell.2016.03.030 .
  14. Toth-Petroczy A, Palmedo P, Ingraham J, Hopf TA, Berger B, Sander C, Marks DS . Structured States of Disordered Proteins from Genomic Sequences . Cell . 167 . 1 . 158–170.e12 . September 2016 . 27662088 . 5451116 . 10.1016/j.cell.2016.09.010 .
  15. Hopf TA, Ingraham JB, Poelwijk FJ, Schärfe CP, Springer M, Sander C, Marks DS . Mutation effects predicted from sequence co-variation . Nature Biotechnology . 35 . 2 . 128–135 . February 2017 . 28092658 . 5383098 . 10.1038/nbt.3769 .
  16. Web site: Feb 17, 2016: ISCB Congratulates 2016 Award Winners, Soren Brunak, Debora Marks, Burkhard Rost, and Serafim Batzoglou. www.iscb.org. July 11, 2016.
  17. Web site: Chan Zuckerberg Science Initiative. Neurodegeneration Challenge Network. 2019-01-01. December 31, 2019. https://web.archive.org/web/20191231184610/http://go.chanzuckerberg.com/ncn. dead.
  18. Web site: April 28, 2022: ISCB Congratulates and Introduces the 2022 Class of Fellows! . www.iscb.org . 17 June 2022.

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