Artificial intelligence for macromolecular analysis and pharmaceutical ligands design

What we are looking for:
We are looking for PhDs in engineering, physics, mathematics, computing science or any related scientific domain with a strong will to apply the AI methods to Structural Biology and Drug Screening. Knowledge of Python and Deep learning libraries are a must. Previous knowledge of Bioinformatics or Biology is highly appreciated, although not compulsory. The Postdoc must propose a research proposal aligned to the presented challenge.

The context:
Structural biology is key to understanding biological macromolecules like proteins and nucleic acids, crucial for biological functions and diseases. Cryo-electron microscopy (cryoEM) revolutionizes this field by visualizing macromolecules at near-atomic resolution, facilitating their study in native states. Simultaneously, computational prediction of ligand binding is vital for drug discovery, helping identify therapeutic candidates by how they interact with biomolecules. The synergy of AI tools for cryoEM and ligand prediction accelerates understanding biological systems and developing new treatments.

The problem to address:
The journey from pixelated snapshots to precise atomic models is fraught with computational hurdles, requiring a blend of innovative AI techniques and a deep understanding of molecular landscapes. Parallel to this endeavor is the quest to discover ligands that snugly fit into these newly revealed structures, a critical step in the design of new drugs. This challenge involves sifting through vast chemical libraries to find those rare molecules that can bind with high affinity to target sites on the macromolecule.

Objectives:

  • Elucidating the complex structures of biological macromolecules from CryoEM images.
  • Discover ligands that fit into the structures revealed for new drug design.

Expected Outcomes:

  • Robust algorithms and workflows to tackle both problems.

Systems Manager job position @ Biocomputing Unit

We have a systems manager job position open at the Biocomputing Unit. Get to know it in this post!

biocomputing unit server rack

Description

We are looking for a candidate with a background in Computer Science for the position of Junior Systems Management. You will be part of the team in charge of managing the computing infrastructure of the group, learning how public science development and compute infrastructures work. The tasks include assisting in the deployment and configuration of hardware and scientific software. Once here, you will also be participating in European and national projects related to cloud and open data technologies. The amount and heterogeneity of servers requires someone capable of thinking out of the box and exercise creativity to solve IT problems in complex scenarios.

Location: in person, UAM campus, Madrid

Background

INSTRUCT ERIC is the European Strategic Initiative in the area of Structural Biology. It is organized as a distributed infrastructure with “Instruct Centers” and the BCU hosts the “INSTRUCT Image Processing Center (I2PC)”. The BCU is well known in the area of 3D-EM, with over 200 publications in the area and large contributions to open-source scientific software, like Scipion, Xmipp and 3DBionotes. For further information go to i2pc.es and biocomputingunit.es webpages.

Required skills

  1. Upper cycle in Computer Science related matters (Spanish “FP superior”, BSc, MSc), Mathematics, Engineering, Physics or equivalent are also accepted.
    • (specialties or mentions related to systems and networks management such as Computer Engineering/Systems administration appreciated)
  2. Scripting and orchestrating experience: Bash and Python scripts, YAML (Ansible and similar)
  3. Experience and commodity in Linux environments (HPC environments is a plus)
  4. Interest and/or experience in computer hardware and computer networks
  5. Medium level of proficiency in written and spoken English

Although not essential, we consider the following skills a “plus”:

  1. Experience in assisting open-source software development teams (GitHub, documentation, user support, collaboration tools…).
  2. Experience in Virtualization: Docker, Virtualbox
  3. Familiarity with the architecture and functioning of GPUs: NVIDIA CUDA, CUDA Toolkit, NVCC…
  4. Experience in Cloud (Amazon AWS)

Applying

Are you interested in our Junior Systems Manager job position? Send your CV and a letter of interest to blanca@cnb.csic.es.

PhD position in Single Particle Analysis and CLEM Correlative Imaging.

Description: We are looking for a candidate with a PhD in Computer Science, Mathematics, Engineering, Physics or equivalent with software development skills, preferrably applied to Structural Biology, Biomedical Imaging, or Imaging in general.

The candidate will work on the development of image processing algorithms for Single Particle Analysis (especially, continuous heterogeneity analysis) and CLEM Correlative imaging (especially, image alignment and segmentation). The contract is for 4 years and will be developed along with Dr. Eva Nogales (from Univ. Calif. Berkeley) in the context of the JAE-CHAIR grant “ALLCRYO. Technical developments for the improvement of the cryoEM workflow, and their application for the structural characterisation of conformationally and compositionally heterogeneous samples in vitro and in vivo.

Location: Madrid

Required Skills:

  • PhD in Computer Science, Mathematics, Engineering, Physics or equivalent
  • Programming experience with Python
  • Experience in Linux
  • Experience in Structural Biology, Biomedical Imaging, General Imaging or Bioinformatics

Interested candidates should send their CV’s and letter of interest to i2pc@cnb.csic.es

PhD position in fluorescence microscopy image processing.

The Biocomputing Unit of the National Biotechnology Centre is looking for excellent master students in Engineering, Physics, Mathematics or any other field related to data analysis. The PhD would be in fluorescence microscopy image processing.

This project involves several fast-growing technologies: electron cryo-microscopy and deep learning. Our laboratory is located at the Centro Nacional de Biotecnología in Madrid, a reference institute in Spain in cryo-EM, with highly advanced fluorescence microscopy facilities. Moreover, our group is a world reference in this field. In this work we intend to follow two main lines of work:

  • Spatio-temporal analysis, which will allow a more accurate detection and quantification of dynamic phenomena at the cellular level, thus facilitating the exploration of complex biological processes in real time
  • Correlative microscopy: To implement and refine correlative microscopy techniques to efficiently integrate data obtained through different fluorescence microscopy modalities, as well as scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

Latest publications

  1. Cayuela, P. Conesa, A. Oña, J.A. Gómez-Pedrero, C.O.S. Sorzano. Real-Time Correction of Chromatic Aberration in Optical Fluorescence Microscopy. Methods and Applications in Fluorescence, 11: 045001 (2023)
  2. Cayuela-López, J.A. Gómez-Pedrero, A.M. Oña Blanco, C.O.S. Sorzano. Cell-TypeAnalyzer: A flexible Fiji/ImageJ plugin to classify cells according to user-defined criteria. Biological Imaging, 2: e5 (2022)
  3. Cayuela, E. García-Cuesta, J.A. Gomez-Pedrero, S.R. Gardeta, J.M. Rodriguez-Frade, M. Mellado, C.O.S. Sorzano. TrackAnalyzer: A Toolbox for a holistic analysis of Single-Particle Tracks. Biological Imaging, 3: e18 (2023)

Interested candidates should send their CV’s and letter of interest to: blanca@cnb.csic.es or coss@cnb.csic.es

New position open: Software Developer in the Biocomputing Unit (BCU), Instruct Image Processing Center (I2PC), Madrid

Description: We are looking for a candidate with a BSc/MSc in Computer Science, Mathematics, Engineering, Physics or equivalent with software development skills. The candidate will be involved in European and National projects related to cloud and open data technologies, being part of a team in charge of developing data management software for Instruct facilities.

Thus, the candidate will participate in projects that will shape and influence strategies for making research data generated across the Instruct-ERIC infrastructure FAIR (Findable, Accessible, Interoperable, Reusable). This data transformation will involve considerations of the storage, metadata description and deposition of large datasets for use and reuse including artificial intelligence. These data will come primarily from structural biology but can include data from other diverse research domains.

Background: INSTRUCT ERIC is the European Strategic Initiative in the area of Integrative Structural Biology. It is organized as a distributed infrastructure with “Instruct Centers” and the BCU hosts the “INSTRUCT Image Processing Center (I2PC)”.

 BCU is well known in the area of 3D-EM, with over 200 publications in the area of Electron Microscopy and large contributions to open source scientific software, like Scipion, Xmipp and 3DBionotes.

For further information go to INSTRUCT Image Processing Center or  Biocomp web sites.

Location: Madrid 

Required Skills:

  • BSc / MSc in Computer Science, Mathematics, Engineering, Physics or equivalent
  • Programming experience with Python
  • Experience in Linux
  • Medium level of proficiency in written and spoken English

The following skills are considered a “plus”, but are not essential:

  • Experience of the full lifecycle of software architecture, design, and implementation
  • Experience developing web and desktop Python apps
  • Knowledge and some degree of experience using relational and/or noSQL databases.
  • Experience in assisting open source software development teams (GitHub, documentation, user support, collaboration tools…).
  • Interest or experience in scientific data management
  • Interest or experience in biological sciences or bioinformatics
  • Experience in Virtualization: Docker

nterested candidates should send their CV’s and letter of interest to i2pc@cnb.csic.es

I2PC – Instruct-RI Hubs hybrid course on Electron Tomography and Subtomogram Averaging. Madrid, December 10 – 13, 2024

VENUE

Hybrid course.
December 10 – 13, 2024 from 16:00 to 21:30 CET.
You do not need to install any special software to connect. A modern browser should be enough.

Overall aims and course outline

By using image processing algorithms, it becomes possible to pinpoint the macromolecules of interest within the electron tomograms. Subsequently, researchers can extract small subtomograms from these locations and identify similar particles, facilitating their averaging and the recognition of diverse conformations. This process, referred to as subtomogram averaging, has played a pivotal role in elucidating an increasing number of macromolecular structures, achieving resolutions ranging from 20 to 3 A.

The course is designed to offer a comprehensive overview of the whole image processing workflow in Electron Tomography (ET). This includes tasks such as aligning the tilt series, reconstructing 3D tomograms, identifying particles, performing subtomogram averaging or even to perform a tomogram segmentation, all inside Scipion integration framework.  

With the experience gained in the organisation of virtual and in-person courses, we intend to organise this course in a hybrid format. We will be able to accommodate up to 20 individuals for in-person attendance. However, other 20 participants will attend remotely. In total, we can host 40 attendees. 

The course is aimed at researchers of all levels wanting to adopt electron microscopy as one of the tools at their disposal for elucidating biological structures

For more information see:

I2PC – Instruct-RI Hubs hybrid course on Electron Tomography and Subtomogram Averaging. Madrid, December 10 – 13, 2024 – I2PC – Instruct Image Processing Center

Position Open in image processing for Cryo-Electron Microscopy at BCU

The Biocomputing Unit (BCU) of the Natl. Center of Biotechnology is looking for a candidate with a background in Engineering, Physics, Mathematics or any other data analysis related field. The work is about the development of image processing in Cryo-Electron Microscopy (CryoEM) with a special emphasis on signal processing and efficient implementations. Our laboratory is located at the National Center of Biotechnology in Madrid, a reference institute in Spain in cryo-EM equipped with two microscopes with direct detector (Talos Arctica and CryoARM 300) and a FIB-SEM microscope, providing a very immersive and interdisciplinary environment. Additionally, our group is a world reference in this domain, and the work will be performed in conjunction with an American/Canadian drug discovery company. The goal of the project is to construct the most efficient 3D reconstruction algorithm available for CryoEM.

Recent publications:

FSC-Q: a CryoEM map-to-atomic model quality validation based on the local Fourier shell correlation. Ramírez-Aportela E, Maluenda D, Fonseca YC, Conesa P, Marabini R, Heymann JB, Carazo JM, Sorzano COS. Nat Commun. 12(1):42. 2021.
DOI: https://doi.org/10.1038/s41467-020-20295-w

Measuring local-directional resolution and local anisotropy in cryo-EM maps. Vilas JL, Tagare HD, Vargas J, Carazo JM, Sorzano COS. Nat Commun. 11(1):55. 2020.
DOI: https://doi.org/10.1038/s41467-019-13742-w

Continuous flexibility analysis of SARS-CoV-2 spike prefusion structures. Melero R, Sorzano COS, Foster B, Vilas JL, Martínez M, Marabini R, Ramírez-Aportela E, Sanchez-Garcia R, Herreros D, Del Caño L, Losana P, Fonseca-Reyna YC, Conesa P, Wrapp D, Chacon P, McLellan JS, Tagare HD, Carazo JM. IUCrJ. 7(Pt 6):1059-69. 2020.
DOI: https://doi.org/10.1107/S2052252520012725

Measurement of local resolution in electron tomography. Vilas JL, Oton J, Messaoudi C, Melero R, Conesa P, Ramirez-Aportela E, Mota J, Martinez M, Jimenez A, Marabini R, Carazo JM, Vargas J, Sorzano COS. J Struct Biol X. 4:100016. 2019
DOI: https://doi.org/10.1016/j.yjsbx.2019.100016

DeepRes: a new deep-learning- and aspect-based local resolution method for electron-microscopy maps. Ramírez-Aportela E, Mota J, Conesa P, Carazo JM, Sorzano COS. IUCrJ. 6(6): 1054 – 1063. 2019
DOI: https://doi.org/10.1107/S2052252519011692

Interested candidates should send their CV’s and letter of interest to: blanca@cnb.csic.es

PhD. position in image processing for Cryo-Electron Microscopy

The Biocomputing Unit of the Natl. Center of Biotechnology is looking for excellent master students in Engineering, Physics, Mathematics or any other data analysis related field that can compete for FPU fellowships: (https://www.educacionyfp.gob.es/servicios-al-ciudadano/catalogo/general/99/998758/ficha/998758-2020.html). The Ph.D. would be about the development of deep learning methods for image processing in Cryo-Electron Microscopy. This project involves several quickly growing technologies: cryo-electron microscopy and deep learning. Our laboratory is located at the National Center of Biotechnology in Madrid, a reference institute in Spain in cryo-EM equipped with two microscopes with direct detector (Talos Arctica and CryoARM 300) and a FIB-SEM microscope, providing a very immersive and interdisciplinary environment. Additionally, our group is a world reference in this domain.

Recent publications:

(1) FSC-Q: a CryoEM map-to-atomic model quality validation based on the local Fourier shell correlation. Ramírez-Aportela E, Maluenda D, Fonseca YC, Conesa P, Marabini R, Heymann JB, Carazo JM, Sorzano COS. Nat Commun. 12(1):42. 2021

DOI: https://doi.org/10.1038/s41467-020-20295-w

(2) Measuring local-directional resolution and local anisotropy in cryo-EM maps. Vilas JL, Tagare HD, Vargas J, Carazo JM, Sorzano COS. Nat Commun. 11(1):55. 2020

DOI: https://doi.org/10.1038/s41467-019-13742-w

(3) Continuous flexibility analysis of SARS-CoV-2 spike prefusion structures. Melero R, Sorzano COS, Foster B, Vilas JL, Martínez M, Marabini R, Ramírez-Aportela E, Sanchez-Garcia R, Herreros D, Del Caño L, Losana P, Fonseca-Reyna YC, Conesa P, Wrapp D, Chacon P, McLellan JS, Tagare HD, Carazo JM. IUCrJ. 7(Pt 6):1059-69. 2020

DOI: https://doi.org/10.1107/S2052252520012725

(4) Measurement of local resolution in electron tomography. Vilas JL, Oton J, Messaoudi C, Melero R, Conesa P, Ramirez-Aportela E, Mota J, Martinez M, Jimenez A, Marabini R, Carazo JM, Vargas J, Sorzano COS. J Struct Biol X. 4:100016. 2019

DOI: https://doi.org/10.1016/j.yjsbx.2019.100016

(5) DeepRes: a new deep-learning- and aspect-based local resolution method for electron-microscopy maps. Ramírez-Aportela E, Mota J, Conesa P, Carazo JM, Sorzano COS. IUCrJ. 6(6): 1054 – 1063. 2019

DOI: https://doi.org/10.1107/S2052252519011692

 

Interested candidates should send their CV’s and letter of interest to: blanca@cnb.csic.es

Position Open: Bioinformatician at Biocomputing Unit CNB

The Biocomputing Unit (BCU) of the National Center for Biotechnology, headed by Drs. Jose Maria Carazo and Carlos Oscar Sanchez Sorzano, works in the area of both experimental and computational structural biology, coordinating Spanish efforts in the European Infrastructure for Integrative Structural Biology Instruct-ERIC

We develop new ways to extract and integrate biomedical information with a structural focus. In particular, and in the context of this position, we develop an integrative environment where both structural models and cryo Electron Microscopy maps are put in the context of multiple other pieces of information as part of an ELIXIR Recommended Interoperability Resource. 

We are looking for a Bioinformatician participating in the development of key components of our Structural Biology tools, specially 3DBionotes

  • Adding new features to
    the platform focusing on added value to a broad spectrum of users.
  • Searching for new data
    sources, dealing with their integration with current data and proposing
    new ways of representation will cover much of the time.
  • Interacting with current
    and potential users.
  • Frequent planning and
    coordination meetings with the rest of the team are expected.
  • Writing reports and
    instruction manuals as well as presenting results to Projects stakeholders
    and the general public will regularly occur.

Required skills:

  • BSc, MSc level or
    equivalent qualification in Bioinformatics, Information Technology,
    Computer Science or a related discipline.
  • Proficiency using a
    command line UNIX/Linux environment.
  • Familiar with main
    programming languages: Python, JavaScript, Ruby.
  • Knowledge of Docker or
    other containerization technologies.
  • Experience of working
    with a high volume of data.
  • Excellent communication
    and presentation skills, including strong written and verbal communication
    in English.

The following skills are
considered a “plus”, but are not essential:

  • Knowledge of Structural biology
    and willingness to stay up-to-date.
  • Experience in data
    analysis, reporting and visualization.
  • Knowledge and some degree
    of experience using relational and/or noSQL databases.
  • Web development
    experience.
  • Familiar with producing
    consuming Web Services.
  • Experience with
    international, multi-disciplinary projects.
  • Analytical mind, eager to
    learn and flexible to adapt to a result driven environment.
  • Ability to work both
    independently and as part of a team.

Interested candidates should send their CV’s and letter of interest to: blanca@cnb.csic.es

Post-doctoral position in STA and SPA image processing.

One is funded by the European Research Council (ERC) and studies EGFRs and associated complexes on the cell membrane. EGFR is a membrane protein of around 200 kDa involved in breast cancer and a target for new therapies. In this study our collaborators at Zurich-ETH produce cryo-ET tilt-series which are then transferred to Madrid for their further image processing analysis.

The other project focuses on the structural analysis of CoV2 variants mapping on the Spike, mostly by Single Particle Analysis methods. The Biocomputing Unit excels in the development of new image processing approaches to tackle hard problems (see some enclosed recent publications).

We are looking for experienced researchers at the postdoc level experts in SPA and subtomogram averaging who would be responsible for image processing (for EGFR) and data collection and image processing (for CoV2), working side by side with other colleagues either developing new image processing methods in XMIPP or engaged in software integration projects in Scipion. Our laboratory is located at the National Center of Biotechnology in Madrid, a reference institute in Spain in cryo-EM equipped with two microscopes with direct detector (Talos Arctica and CryoARM 300) and a FIB-SEM microscope, providing a very immersive and interdisciplinary environment.

Recent publications:

  1. FSC-Q: a CryoEM map-to-atomic model quality validation based on the local Fourier shell correlation. Ramírez-Aportela E, Maluenda D, Fonseca YC, Conesa P, Marabini R, Heymann JB, Carazo JM, Sorzano COS. Nat Commun. 12(1):42. 2021
    DOI: https://doi.org/10.1038/s41467-020-20295-w
  2. Measuring local-directional resolution and local anisotropy in cryo-EM maps. Vilas JL, Tagare HD, Vargas J, Carazo JM, Sorzano COS. Nat Commun. 11(1):55. 2020
    DOI: https://doi.org/10.1038/s41467-019-13742-w
  3. Continuous flexibility analysis of SARS-CoV-2 spike prefusion structures. Melero R, Sorzano COS, Foster B, Vilas JL, Martínez M, Marabini R, Ramírez-Aportela E, Sanchez-Garcia R, Herreros D, Del Caño L, Losana P, Fonseca-Reyna YC, Conesa P, Wrapp D, Chacon P, McLellan JS, Tagare HD, Carazo JM. IUCrJ. 7(Pt 6):1059-69. 2020
    DOI: https://doi.org/10.1107/S2052252520012725
  4. Measurement of local resolution in electron tomography. Vilas JL, Oton J, Messaoudi C, Melero R, Conesa P, Ramirez-Aportela E, Mota J, Martinez M, Jimenez A, Marabini R, Carazo JM, Vargas J, Sorzano COS. J Struct Biol X. 4:100016. 2019
    DOI: https://doi.org/10.1016/j.yjsbx.2019.100016
  5. DeepRes: a new deep-learning- and aspect-based local resolution method for electron-microscopy maps. Ramírez-Aportela E, Mota J, Conesa P, Carazo JM, Sorzano COS. IUCrJ. 6(6): 1054 – 1063. 2019
    DOI: https://doi.org/10.1107/S2052252519011692

Interested candidates should send their CV’s and letter of interest to: blanca@cnb.csic.es