The INPhINIT “la Caixa” fellowship program is open and we are offering 2 positions.
Position 1: Discovering novel targets for anti-invectives in ribosomal assembly and initiation complexes using cutting-edge cryo-EM methodologies: A path to developing new clinically relevant antibiotics.
Do you dream of glimpsing into the core of a cell and seeing nature’s machines at work making proteins, lipids and other complex molecules? Our ability to realize this dream is rapidly approaching and cryo-electron microscopy (cryo-EM) is one of the biophysical techniques leading the way. The power of cryo-EM was recognized in the 2017 Nobel Prize in Chemistry and has recently undergone a technical revolution hallmarked by a dramatic increase in the resolving power. Until a few years ago, cryo-EM was limited to providing low-resolution structures (10-20 Å) but today cryo-EM has the power to resolve the atomic structure of nature’s biological machines (>3 Å). At this resolution, we can describe the molecular structure of vital macromolecular complexes and understand how their structure changes to elicit a functional activity. Moreover, we can observe substrates bound in catalytic sites and begin to define how interactions and reactive centres drive reactions or promote conformational changes essential to the machine’s cellular role. Understanding these details allows one to harness the activity of the machine for applications in biotechnology (chemical biology) or designing molecules that regulate the activity of the machine for biomedical applications (i.e. antibiotics). The research conducted in the Connell group aims at understanding and further developing the mechanism of action of clinically relevant or newly discovered antibiotics that target the ribosome, one of the most vital macromolecular machine of the cell, devoted to protein synthesis. The prospective student will join a highly collaborative and multi-disciplinary research team to study at the structural level the assembly and initiation phases of protein synthesis to identify targets and describe the mode of action of novel antibiotics with clinical potential. Uncovering the structural basis of antibiotic action can yield solutions to the ever-threatening problem of growing antibiotic resistance.
Our groups are located in the CIC bioGUNE at the heart of the beautiful Basque Country, in Spain. We employ cryo-EM to understand how chemical reactions drive large macromolecular machines with the goal being to regulate the reactions (i.e. develop inhibitors as drugs) and/or harness the synthetic capabilities of these machines for chemical biology (i.e. biotechnology). Ideally, the prospective researcher should have a background in biochemistry, biophysics, biology, chemistry, or other related fields and possess a strong desire to understand biological processes at the molecular level. The researcher will receive training in the Connell/Fucini groups related to the study of novel translational inhibitors that target the translational machinery with the possibility to develop part of the project within a very active network of international collaborations (Germany, UK, Japan, Italy). The highly multi-disciplinary nature of the project will allow the student to receive training in complementary approaches ranging from molecular biology, protein/ribosome purification and biochemistry to state-of-the-art structural biology i.e. NMR, X-ray crystallography and cryo-EM. The prospective researcher will receive training in cryo-EM data acquisition on both our home microscope as well as at national and international cryo-EM facilities (Germany, United Kingdom, Netherlands) to gain access to the most advanced cryo-EM technologies. Training in cryo-EM data processing will be provided by the Connell/Fucini lab and supplemented by participation in international workshops. The researcher will also be trained in the application of high-performance computing and scripting (shell/Python) to cryo-EM. As cryo-EM is a rapidly emerging technique these skills are currently highly sought out in both the academic and industrial sector boosting the research’s future career prospects.
Position 2: Discovering novel targets for anti-invectives in ribosomal assembly and initiation complexes using cutting-edge cryo-EM methodologies: A path to developing new clinically relevant antibiotics.
Since their early discovery and use in the clinical setting, antibiotics have revolutionised modern medicine by making treatable previously incurable illnesses like pneumonia, scarlet fever and tuberculosis as well as supporting or substituting the action of a compromised immune system, enabling the advent of surgery, organ transplant and cancer treatment like chemotherapy and radiotherapy. This idyllic situation is currently under the risk of a dramatic end and a return to the pre-antibiotic era. Indeed, only a few classes of antibiotics have been developed so far and their efficacy, easy access, use and/or even overuse, especially in agriculture, animal and food industry, has lead to the widespread emergence of antibiotic resistance and the rise of bacteria and infections against which no antibiotics have any effect. This alarming situation has prompted the World Health Organization to declare antimicrobial resistance to be one of the greatest threats to human health, urging the search for new and more potent anti-infectiveness.
Our group is actively participating in the discovery of novel antimicrobial agents, establishing complementary approaches to understand and further develop the mechanism of action of clinically relevant or newly discovered antibiotics that target the ribosome, one of the most vital macromolecular complexes of the cell. Currently, we are seeking a talented and motivated PhD student that would join us in this quest. The selected candidate will work in a highly collaborative and multi-disciplinary research team, employing both structural biology and biochemical assays to elucidate the mechanism of action of recently discovered natural products with a strong potential to lead the development of a completely new class of antibiotics.
Do not hesitate to contact us if you want to have more information about this project.
The prospective candidate will join the Fucini group and work in close collaboration with the group of Dr. Connell, also located in the CIC bioGUNE, at the heart of the beautiful Basque Country (Spain). Ideally, the prospective researcher should have a background in biochemistry, biophysics, biology, chemistry, or other related fields and have a strong curiosity to understand biological processes at the molecular level. The researcher will develop the project in collaboration with experienced post-doctoral scientists of the Fucini/Connell groups and receive multi-disciplinary training related to the study of novel inhibitors that target the ribosome. The student will acquire expertise in biochemical approaches to characterise the antibiotic’s inhibitory activity on the translational machinery and in structural biology techniques (i.e. NMR, X-ray crystallography and cryo-EM) to provide a molecular description of the antibiotic/ribosome interaction and its mode of action. The student will have the possibility to register in a PhD program organised by the University of the Basque Country designed for individuals who aspire to a career in academic biomedicine or a leadership role in the biomedical industry. In addition to this training program, the candidate will participate in international workshop and profit from the multidisciplinary nature of the centre, which combines Genomics, Proteomics and Metabolomics platforms with state-of-the-art Structural Biology core facilities. In addition, the prospective researcher will utilize national (ALBA, Barcelona) and international (Diamond, UK) X-ray crystallography and cryo-EM platforms for data collection. The highly multi-disciplinary nature of the project will allow the student to develop part of the project within a very active network of international collaborations (USA, UK, France and Italy) in the academic and industrial sector providing networking opportunities and boosting the researcher’s future career prospects.