Debora Marks

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Debora Marks
Debbie Marks HR.jpg
Debora Marks
Alma mater University of Bristol, University of Manchester, Humboldt University
Awards Overton Prize, Ben Barres Early Career Award
Scientific career
Fields Artificial Intelligence, Structural Biology, Bioinformatics
Institutions Harvard Medical School
Thesis  (2010)
Doctoral advisor Reinhard Heinrich, Hanspeter Herzl
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.

Contents

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 [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 and husband 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]

Related Research Articles

microRNA Small non-coding ribonucleic acid molecule

Micro ribonucleic acid are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in messenger RNA (mRNA) molecules, then silence said mRNA molecules by one or more of the following processes:

<span class="mw-page-title-main">Gene expression</span> Conversion of a genes sequence into a mature gene product or products

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, and ultimately affect a phenotype. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. The process of gene expression is used by all known life—eukaryotes, prokaryotes, and utilized by viruses—to generate the macromolecular machinery for life.

<span class="mw-page-title-main">Non-coding RNA</span> Class of ribonucleic acid that is not translated into proteins

A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as small RNAs such as microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs such as Xist and HOTAIR.

<span class="mw-page-title-main">Regulation of gene expression</span> Modifying mechanisms used by cells to increase or decrease the production of specific gene products

Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products. Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.

<span class="mw-page-title-main">Small interfering RNA</span> Biomolecule

Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded non-coding RNA molecules, typically 20–24 base pairs in length, similar to microRNA (miRNA), and operating within the RNA interference (RNAi) pathway. It interferes with the expression of specific genes with complementary nucleotide sequences by degrading messenger RNA (mRNA) after transcription, preventing translation. It was discovered in 1998 by Andrew Fire at the Carnegie Institution for Science in Washington, D.C. and Craig Mello at the University of Massachusetts in Worcester.

The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which functions in gene silencing via a variety of pathways at the transcriptional and translational levels. Using single-stranded RNA (ssRNA) fragments, such as microRNA (miRNA), or double-stranded small interfering RNA (siRNA), the complex functions as a key tool in gene regulation. The single strand of RNA acts as a template for RISC to recognize complementary messenger RNA (mRNA) transcript. Once found, one of the proteins in RISC, Argonaute, activates and cleaves the mRNA. This process is called RNA interference (RNAi) and it is found in many eukaryotes; it is a key process in defense against viral infections, as it is triggered by the presence of double-stranded RNA (dsRNA).

mir-148/mir-152 microRNA precursor family

In molecular biology, miR-148 is a microRNA whose expression has been demonstrated in human, mouse, rat and zebrafish. miR-148 has also been predicted in chicken.

mir-219 microRNA precursor family

In molecular biology, the microRNA miR-219 was predicted in vertebrates by conservation between human, mouse and pufferfish and cloned in pufferfish. It was later predicted and confirmed experimentally in Drosophila. Homologs of miR-219 have since been predicted or experimentally confirmed in a wide range of species, including the platyhelminth Schmidtea mediterranea, several arthropod species and a wide range of vertebrates. The hairpin precursors are predicted based on base pairing and cross-species conservation; their extents are not known. In this case, the mature sequence is excised from the 5' arm of the hairpin.

Anders Krogh is a bioinformatician at the University of Copenhagen, where he leads the university's bioinformatics center. He is known for his pioneering work on the use of hidden Markov models in bioinformatics, and is co-author of a widely used textbook in bioinformatics. In addition, he also co-authored one of the early textbooks on neural networks. His current research interests include promoter analysis, non-coding RNA, gene prediction and protein structure prediction.

<span class="mw-page-title-main">RNA interference</span> Biological process of gene regulation

RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling. The detailed study of each of these seemingly different processes elucidated that the identity of these phenomena were all actually RNAi. Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNAi in the nematode worm Caenorhabditis elegans, which they published in 1998. Since the discovery of RNAi and its regulatory potentials, it has become evident that RNAi has immense potential in suppression of desired genes. RNAi is now known as precise, efficient, stable and better than antisense therapy for gene suppression. Antisense RNA produced intracellularly by an expression vector may be developed and find utility as novel therapeutic agents.

The ISCB Overton Prize is a computational biology prize awarded annually for outstanding accomplishment by a scientist in the early to mid stage of his or her career. Laureates have made significant contribution to the field of computational biology either through research, education, service, or a combination of the three.

<span class="mw-page-title-main">Steven E. Brenner</span> American biologist and academic

Steven Elliot Brenner is a professor at the Department of Plant and Microbial Biology at the University of California Berkeley, adjunct professor at the Department of Bioengineering and Therapeutic Sciences at the University of California, and San Francisco Faculty scientist, Physical Biosciences at the Lawrence Berkeley National Laboratory.

<span class="mw-page-title-main">Chris Sander (scientist)</span> German computational biologist

Chris Sander is a computational biologist based at the Dana-Farber Cancer Center and Harvard Medical School. Previously he was chair of the Computational Biology Programme at the Memorial Sloan–Kettering Cancer Center in New York City. In 2015, he moved his lab to the Dana–Farber Cancer Institute and the Cell Biology Department at Harvard Medical School.

<span class="mw-page-title-main">Burkhard Rost</span> German computational biology researcher

Burkhard Rost is a scientist leading the Department for Computational Biology & Bioinformatics at the Faculty of Informatics of the Technical University of Munich (TUM). Rost chairs the Study Section Bioinformatics Munich involving the TUM and the Ludwig Maximilian University of Munich (LMU) in Munich. From 2007-2014 Rost was President of the International Society for Computational Biology (ISCB).

<span class="mw-page-title-main">Gary Stormo</span> American geneticist (born 1950)

Gary Stormo is an American geneticist and currently Joseph Erlanger Professor in the Department of Genetics and the Center for Genome Sciences and Systems Biology at Washington University School of Medicine in St Louis. He is considered one of the pioneers of bioinformatics and genomics. His research combines experimental and computational approaches in order to identify and predict regulatory sequences in DNA and RNA, and their contributions to the regulatory networks that control gene expression.

<span class="mw-page-title-main">Dana Pe'er</span> Bioinformatician

Dana Pe'er, Chair and Professor in Computational and Systems Biology Program at Sloan Kettering Institute is a researcher in computational systems biology. A Howard Hughes Medical Institute (HHMI) Investigator since 2021, she was previously a professor at Columbia Department of Biological Sciences. Pe'er's research focuses on understanding the organization, function and evolution of molecular networks, particularly how genetic variations alter the regulatory network and how these genetic variations can cause cancer.

<span class="mw-page-title-main">Alex Bateman</span> British bioinformatician

Alexander George Bateman is a computational biologist and Head of Protein Sequence Resources at the European Bioinformatics Institute (EBI), part of the European Molecular Biology Laboratory (EMBL) in Cambridge, UK. He has led the development of the Pfam biological database and introduced the Rfam database of RNA families. He has also been involved in the use of Wikipedia for community-based annotation of biological databases.

Direct coupling analysis or DCA is an umbrella term comprising several methods for analyzing sequence data in computational biology. The common idea of these methods is to use statistical modeling to quantify the strength of the direct relationship between two positions of a biological sequence, excluding effects from other positions. This contrasts usual measures of correlation, which can be large even if there is no direct relationship between the positions. Such a direct relationship can for example be the evolutionary pressure for two positions to maintain mutual compatibility in the biomolecular structure of the sequence, leading to molecular coevolution between the two positions.

<span class="mw-page-title-main">Hanah Margalit</span>

Hanah Margalit is a Professor in the faculty of medicine at the Hebrew University of Jerusalem. Her research combines bioinformatics, computational biology and systems biology, specifically in the fields of gene regulation in bacteria and eukaryotes.

Rita Casadio is an Adjunct Professor of Biochemistry/Biophysics in the Department of Pharmacy and Biotechnology at the University of Bologna.

References

  1. "Debora S. Marks Lab" . Retrieved July 11, 2016.
  2. 1 2 "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.