Molecular Dynamics Simulations of Genetic Variants – Lal research group
We are seeking people interested in a postdoc or scientist position in structural biology, computational chemistry, and bioinformatics.
The Lal research group focuses on translational genetic research and bioinformatics. Research interests involve developing a comprehensive understanding of how alterations in the genome contribute to disease.
The lab pursues questions such as, “Why did the patient develop this disease?” “Will the patient respond to this medication?” “Can we predict the disease prognosis?” “What is the underlying mechanism?” We have published ~90 publications in the last six years, several in prestigious journals such as PNAS, Nature Genetics, Lancet Neurology, Annals of Neurology, Bioinformatics, Genome Medicine, Nuclei Acid Research, and Brain. A complete list of recent studies can be found in pubmed: https://pubmed.ncbi.nlm.nih.gov/?term=Dennis+lal&show_snippets=off&sort=date&size=100 .
The candidate will be integrated within the Genomic Medicine Institute of the Cleveland Clinic to perform translational genetics research. The position will be at the Lerner Research Institute of the Cleveland Clinic. The team is closely collaborating with other data scientists, neuroscientists, and epileptologists, and clinical researchers from related fields.
Besides local collaborations, the team will interact on a daily to weekly basis with the Lal research groups at the Broad Institute of MIT and Harvard and the Cologne Center for Genomics in Germany.
Specifically, we are looking for a new member analyzing mutated amino acids on 3D protein structures, performing homology modeling, and molecular dynamics analyses at medium and large scale. Our team has extensive experience in genomics, bioinformatics, data science, software engineering, neuroscience, and protein structural biology. However, our team has limited knowledge in molecular dynamics modeling, and the candidate should have extensive experience on this topic to add value to interdisciplinary projects.
Ph.D. degree in Bioinformatics, Biology, Biochemistry, or other relevant scientific discipline or equivalent experience.
Extensive experience with tools related to:
-Molecular dynamics simulation
-Examples include: CHARMM, GROMACS, FoldX, MOE, Schrodinger, Rosetta, Discovery Studio, PyMOL
Basic programming skills in one of the following coding languages: Python, R, Bash, Java, or C++
Self-starter, highly motivated
At least one published first author publication (preprint or pubmed).
WHAT WE OFFER:
-The chance to have a real impact on the advancement of science and medicine. We work closely with clinicians, family foundations and industry -partners.
-We offer great mentoring and support in career development. Previous postdocs were successful in acquiring faculty and industry job positions of their choice.
-You will learn a lot from other members of the team who are working on a wide-range of projects. Members of our team have a diverse background including genomics, biology, bioinformatics, software development, economics, structural biology and we interact daily with neuroscientists, pediatric neurologists, epileptologists, computational chemists, gene therapy scientists, statisticians and pathologists.
-Opportunities to participate in training workshops and present results at national and international meetings.
-A good working environment in a fun team.
Dr. Dennis Lal; firstname.lastname@example.org
Selected studies from the team:
Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants.
Iqbal S, Pérez-Palma E, Jespersen JB, May P, Hoksza D, Heyne HO, Ahmed SS, Rifat ZT, Rahman MS, Lage K, Palotie A, Cottrell JR, Wagner FF, Daly MJ, Campbell AJ, Lal D.Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28201-28211. doi: 10.1073/pnas.2002660117. Epub 2020 Oct 26
MISCAST: MIssense variant to protein StruCture Analysis web SuiTe.
Iqbal S, Hoksza D, Pérez-Palma E, May P, Jespersen JB, Ahmed SS, Rifat ZT, Heyne HO, Rahman MS, Cottrell JR, Wagner FF, Daly MJ, Campbell AJ, Lal D.Nucleic Acids Res. 2020 Jul 2;48(W1):W132-W139. doi: 10.1093/nar/gkaa361.
A catalogue of new incidence estimates of monogenic neurodevelopmental disorders caused by de novo variants.
López-Rivera JA, Pérez-Palma E, Symonds J, Lindy AS, McKnight DA, Leu C, Zuberi S, Brunklaus A, Møller RS, Lal D.Brain. 2020 Apr 1;143(4):1099-1105. doi: 10.1093/brain/awaa051.
Identification of pathogenic variant enriched regions across genes and gene families.
Pérez-Palma E, May P, Iqbal S, Niestroj LM, Du J, Heyne HO, Castrillon JA, O’Donnell-Luria A, Nürnberg P, Palotie A, Daly M, Lal D.Genome Res. 2020 Jan;30(1):62-71. doi: 10.1101/gr.252601.119. Epub 2019 Dec 23.
Epilepsy subtype-specific copy number burden observed in a genome-wide study of 17 458 subjects.
Niestroj LM, Perez-Palma E, Howrigan DP, Zhou Y, Cheng F, Saarentaus E, Nürnberg P, Stevelink R, Daly MJ, Palotie A, Lal D; Epi25 Collaborative.
Brain. 2020 Jul 1;143(7):2106-2118. doi: 10.1093/brain/awaa171.
Simple ClinVar: an interactive web server to explore and retrieve gene and disease variants aggregated in ClinVar database.
Pérez-Palma E, Gramm M, Nürnberg P, May P, Lal D.
Nucleic Acids Res. 2019 Jul 2;47(W1):W99-W105. doi: 10.1093/nar/gkz411.
Polygenic burden in focal and generalized epilepsies.
Leu C, Stevelink R, Smith AW, Goleva SB, Kanai M, Ferguson L, Campbell C, Kamatani Y, Okada Y, Sisodiya SM, Cavalleri GL, Koeleman BPC, Lerche H, Jehi L, Davis LK, Najm IM, Palotie A, Daly MJ, Busch RM; Epi25 Consortium, Lal D.
Brain. 2019 Nov 1;142(11):3473-3481. doi: 10.1093/brain/awz292.
De novo variants in neurodevelopmental disorders with epilepsy.
Heyne HO, Singh T, Stamberger H, Abou Jamra R, Caglayan H, Craiu D, De Jonghe P, Guerrini R, Helbig KL, Koeleman BPC, Kosmicki JA, Linnankivi T, May P, Muhle H, Møller RS, Neubauer BA, Palotie A, Pendziwiat M, Striano P, Tang S, Wu S; EuroEPINOMICS RES Consortium, Poduri A, Weber YG, Weckhuysen S, Sisodiya SM, Daly MJ, Helbig I, Lal D, Lemke JR.
Nat Genet. 2018 Jul;50(7):1048-1053. doi: 10.1038/s41588-018-0143-7. Epub 2018 Jun 25.
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