Dr Caro RossDr Caroline Ross
caro.ross@uct.ac.za 

Dr. Caroline Ross is an RNA biologist specialising in the integration of computational and experimental approaches to explore the complexities of gene regulation. She is a new lecturer in the Department of Molecular and Cell Biology at the University of Cape Town. Caroline earned her PhD in structural bioinformatics from Rhodes University in South Africa and Sabancı University in Istanbul, Turkey. Her doctoral research focused on modeling the structural dynamics and protein interactions of enterovirus capsids to elucidate hotspots that mediate the conformational changes underlying viral uncoating and genome release, for novel antiviral drug discovery.

Currently, Caroline’s research investigates the complexities of the noncoding genome and its implications for gene regulation across a diverse array of organisms, from mammals to fungal pathogens. Her primary objective is to elucidate the regulatory roles of long noncoding RNAs (lncRNAs) in key cellular processes and to unravel the intricate mechanisms governing their functions. Her work addresses the pressing question of how the
functionalities of lncRNAs are encoded in their rapidly evolving sequences, with the ultimate goal of developing targeted RNA-based therapies to disrupt lncRNA activity in disease-relevant contexts, particularly rare neurodevelopmental disorders. This current focus expands on her postdoctoral work at the Weizmann Institute of Science, where she investigated the functions and evolution of lncRNAs in Igor Ulitsky's lab.

Prospective projects for 2025
See below

Bioinformatics Tools

LncLOOM - a graph-based framework that uses integer programming to identify combinations of short motifs that are deeply conserved in rapidly evolving sequences. It is implemented in Python 2 and Python 3 and is supported on Linux/Unix-based systems https://github.com/lncLOOM/lncLOOM 

MODE-TASK -     a collection of tools for analysing normal modes and performing principal component analysis of macromolecole dynamics. Implemented in Python 3, with additional scripts in C++ https://github.com/RUBi-ZA/MODE-TASK 

Selected publications

C.J Ross and Igor Ulitksy, Patent IL303753A : Compositions for use in the treatment of chd2 haploinsufficiency and methods of identifying same. RNA-based antisense oligonucleotides that target CHASERR lncRNA to boost Chd2 levels, and the lncLOOM algorithm invented to predict ASO target sites.

X. Sabaté-Cadenas, P. Lavalou, C.J Ross, L. Chen, D. Zielinski, S. Larcher, T. Larcher, M. Petitjean, L. Damy, N. Servant, I. Bièche, I. Ulitsky, A. Shkumatava, 2024, Conserved RNA-binding protein interactions mediate syntologous lncRNA functions, Under revision in Nature Communications, BioRxiv. https://doi.org/10.1101/2024.08.21.605776

C.J Ross and I. Ulitsky, 2022, Discovering functional motifs in long noncoding RNAs, WIREs RNA. https://doi.org/10.1002/wrna.1708

C.J. Ross; A. Rom; A. Spinrad; D. Gelbard Solodkin; N. Degani; I. Ulitsky, Jan 2021,Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences, Genome Biology 1(22), p. 29. Number of citations 44. https://doi.org/10.1186/s13059-020-02247-1

A. Khairallah, C.J. Ross, Ö. Tastan Bishop, 2021, GTP Cyclohydrolase I as a Potential Drug Target: New Insights into Its Allosteric Modulation via Normal Mode Analysis. J Chem Inf Model, 27;61(9):4701-4719. https://pubs.acs.org/doi/10.1021/acs.jcim.1c00898

A. Khairallah, C.J. Ross, Ö. Tastan Bishop, 2020, Probing the Structural Dynamics of the Plasmodium falciparum Tunneling-Fold Enzyme 6-Pyruvoyl Tetrahydropterin Synthase to Reveal Allosteric Drug Targeting Sites. Front Mol Biosci. 25;7:575196..  https://doi.org/10.3389/fmolb.2020.575196 

N. Upfold, C. Ross, Ö.Tastan Bishop and C. Knox, 2020, The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus Capsid, Viruses 12(4), 387;  https://doi.org/10.3390/v12040387

C. Ross, B. Nizami, M. Glenister, O.S. Amamuddy, A.R. Altigan, C. Atilgan and Ö.Tastan Bishop, 2018, MODE-TASK: Large-scale protein motion tools. Bioinformatics, bty427, Number of citations 49. https://doi.org/10.1093/bioinformatics/bty427

C. Ross, A.R. Altigan, Ö. Tastan Bishop and C. Atilgan, 2018, Unravelling the motions behind Enterovirus 71 Uncoating, Biophysical Journal 114(4), pp.822-838, Number of citations 21. doi: https://doi.org/10.1016/j.bpj.2017.12.021

N. Upfold, C. Ross, Ö.Tastan Bishop, G. Luke and C. Knox, 2018, The generation and characterisation of neutralising antibodies against the Theiler’s murine encephalomyelitis virus (TMEV) GDVII capsid reveals the potential binding site of the host cell co-receptor, heparan sulfate, Virus Research 244), pp 153-163. https://doi.org/10.1016/j.virusres.2017.11.017

C. Ross, C. Knox and Ö. Tastan Bishop, 2017, Interacting motif networks located in hotspots associated with RNA-release are conserved in enterovirus capsids, FEBS Letters. https://febs.onlinelibrary.wiley.com/doi/abs/10.1002/1873-3468.12663

D.K. Brown, D.L. Penkler, O.S. Amamuddy, C. Ross, A.R. Atilgan, C. Atilgan and Ö. Tastan Bishop, 2017, MD-TASK: a software suite for analyzing molecular dynamics trajectories, Bioinformatics 33(17), pp 2768 – 2771, Number of citations 162 https://doi.org/10.1093/bioinformatics/btx349 

International Conference Talks

Targeting CHASERR long noncoding RNA to boost levels of CHD2. Presented at: Coalition to Cure CHD2’s Inaugural Family and Scientific Conference on CHD2-related disorders, Lake Buena Vista, Florida, USA, June 2023

Decoding the functional importance of sparse highly conserved short motifs in lncRNA genes, Presented at: ILANIT | FISEB Experimental Biology Conference 2023, Eilat, Israel, February 2023

Uncovering deeply conserved motif combinations in rapidly evolving sequences with LncLOOM. Presented at: EMBO YIP virtual RNA/Structural Biology sectoral meeting, August 2020

A graph-based approach for identifying conserved element combinations in long noncoding RNAs. Presented at: RNA Informatics, September 2019, Wellcome Genome Campus Conference Centre, Hinxton, Cambridge, UK

Unravelling the motions behind Enterovirus 71 Uncoating, Highlight Track. Presented at: European Conference for Computational Biology (ECCB), September 2018,  Athens, Greece

Structural based prediction of novel linear B-cell epitopes in picornaviruses. Presented at: From Computational Biophysics to Systems Biology (CBSB), May 2016, Ankara, Turkey

In Silico Analysis of Evolutionary Conserved Interacting Motifs within Picornavirus Capsids. Presented at: Biophysics in the understanding, diagnosis and treatment of infectious diseases, November 2015, Stellenbosch, South Africa

Prospective projects for 2025

Dr Caroline Ross, is offering MSc/PhD projects in computational biology. Although experience with coding or structural bioinformatics will be advantageous, a good understanding of chemistry or mathematics will also provide a strong starting point. However, Dr Ross will work closely with her students to teach them the bioinformatics concepts. As such, students with no prior computational experience are welcome to talk to Dr Ross about taking on one of the projects - if they have a strong interest in learning bioinformatics .
 
The projects range as follows, with an underlying theme of drug discovery and RNA-based therapeutics. 
 

  1. Novel drug discovery against pathogenic fungi - specifically targeting proteins in Candida species. This work will involve protein modelling, structural analysis of SNPs, and molecular dynamics to understand the mechanism of various proteins. This will be followed by computational screening of natural and other small compounds that have the potentital to selectively inhibit these proteins.
  2. Decoding the evolution of long noncoding RNAs across multiple species of fungal pathogens. This project will involve the large scale assembly of transcriptomes from public RNA-seq and meta-transcriptomic data, followed by sequence analysis to identify functionally important RNA elements that can serve as novel drug targets.
  3. Analysis of the sequence elements and chromatin environment that mediates alternative polyadenylation and the formation of fusion proteins - towards designing novel RNA therapies to treat rare neurological disease.
  4. Elucidating the role of the noncoding genome in neuropsychiatric disorders. Primary aims are identify key loci and to derive testable hypothesis that will allow us to design targeted RNA therapies. This project will involve the large-scale analysis of RNA-seq data, whole genome sequencing, Hi-C (3D organisation of the genome), and structural rearrangements. 

If you are interested, please send an email to Dr Ross caro.ross@uct.ac.za.