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The age-related changes in hematopoiesis (ARCH) project is part of the Innovative Training Network (ITN) of the Marie-Sklodowska Curie Actions (MSCA) program, which provides doctorate training of excellence based on the exchange of ideas and competencies from the academic and private sectors.1 The ARCH project intends to outline hematopoietic stem cell (HSC) alterations with aging, how hematopoietic cell individuality is controlled at the transcriptional and epigenetic levels in normal hematopoiesis and in leukemias, and understand the crosstalk between intrinsic and extrinsic indications that support the proliferation of preleukemic and leukemic cells within the hematopoietic niche. We are 15 PhD students funded by this network, based around Europe, and our common aim is to understand functional changes in the hematopoietic system with age, how these changes link to the development of age-associated diseases and in parallel work towards the development of new treatments.2 Our projects kicked off just when the severe acute respiratory coronavirus-2 (SARS-CoV-2) emerged. Two and a half years later, SARS-CoV-2 continues to infect millions of people and has taken the lives of at least 6 million people worldwide.3 The COVID-19 outbreak brought along social isolation and feelings of uncertainty to everyone around the world, including doctorate students.4,5 Ironically, our projects have been more relevant than ever, as the pandemic has highlighted the important relationship between age-related changes in hematopoiesis and disease severity. Below, we aim to discuss the timeline of the ARCH project throughout the pandemic and how we managed to courageously pull through the hardships of doing research during a global pandemic within different settings (academia/institutes and industry). We provide recommendations to future PhD students on how to manage their PhD projects during global emergencies. PANDEMIC TIMELINE OF ARCH The rapid spread of SARS-CoV-2 at the beginning of 2020 in Europe led the World Health Organization to declare a global pandemic on March 11, 2020. The ARCH opening conference, planned for the same month was canceled. At the same time, the first lockdowns were put in place around Europe, while most of us were just starting our new project or were moving to a different country to begin. Some of us started on this project during or after the first lockdown, causing further delays, which led to a multiphasic pattern of recruitment (Figure 1). During the first lockdown, we individually set up our strategies to progress our research projects at home by either reading scientific literature, writing review papers,6-9 or planning experiments for when we would eventually return to work. By summer 2020, many of us began to slowly get back to the laboratory in shifts or for a limited time to avoid overcrowding of spaces. Times were still uncertain and the pandemic was of great concern to the global scientific community. With the whole world waiting for vaccine developments to stop the pandemic, our slow training process commenced. However, by fall, new lockdown measures were set against a new surge of infections and deaths (Figure 1). This second lockdown stretched until Christmas, marking the completion of our first year with minimal hands-on training and very limited experimental progress. This brings us to today, where most of us have entered the final year of our projects and it seems that COVID-19 is here to stay.Figure 1.: Timeline of the ARCH project during the COVID-19 pandemic. Average 14-day notification rates of newly reported COVID-19 cases per 100,000 inhabitants and COVID-19 related deaths per 1 million inhabitants in the participating countries of the ARCH project are represented during the first year and a half of the pandemic in Europe (top graph). By fall 2020, there is an all-time high of the infection and death rates. The lockdown frequency considered as the daily number of ARCH participating countries under measurements of lockdown is shown in a heat-map along the same period (middle graph). Starting time and country of the beneficiary institution where each early stage researcher (ESR) performs the PhD project is shown in bars (bottom graph). These data have been collected from official governmental reports from each country. The lockdown definition and concrete measures differ between countries and regions within the countries.COVID-19: PHDS INTO THE UNKNOWN Engaging in a PhD project on its own is stressful and overwhelming. The main objectives when beginning a 3-year PhD project are to develop new laboratory, academic, and research-based skills, yet we were unable to advance on any of these. Close and continuous supervision is required to meet these goals. Communication with supervisors at the beginning of our PhDs, which coincided with the pandemic, made our start more challenging than expected. Coming out of isolation in the summer of 2020, we did not expect those upcoming months would continue to affect our projects and to make us experience how vulnerable we are. Working hours were adjusted to allow for social distancing, while meetings were still being held online. Even when we were physically at the laboratory, there was an inability for close supervision due to safety restrictions. In addition to communication challenges, technical difficulties were also at play during the first lockdown. For example, students that had already begun to breed mice a few weeks before the lockdown were forced to interrupt their experiments and redirect their projects as it would take too much time to re-establish mouse breeding. The high demand for equipment, reagents, and consumables for the advancement of COVID-19 research and diagnosis added to these difficulties and made it challenging for us to obtain the necessary consumables for our research. Reagents and consumables were not the only shortage, but also sample availability. As our projects are based on hematology, many of our experiments require fresh samples from healthy or diseased participants to progress. Such fresh materials were merely impossible to find as clinics halted unnecessary visits and hospitals gave sole priority to COVID-19 patients. Again, this inevitably led to the redirection of some projects and added to the uncertainties and delays of the projects. Some institutions acknowledged the loss of time for many PhD students and offered time extensions for thesis submissions. In some institutions, time extensions were only applicable to students that were enrolled in their second and third year, a situation that we consider is not justified as the pandemic had a strong impact on all PhD projects regardless of the year of enrollment. However, those that were offered an extension were offered no additional financial support. This made us feel that our PhD training status was overlooked and shows once more that PhD positions are a precarious form of employment. As these are typically 3 to 4 year training periods, where PhD students need to provide evidence of strong scientific skills, not being able to work is a major limitation not only to obtain the PhD degree, but also for the success in making next step in the career. COVID-19 repercussions created disruptions also to life science companies. Twenty percent of ARCH students work in the private sector. Companies had to adapt to the COVID-19 pandemic to survive, thus made COVID-19 research and treatment innovation their uppermost priority. Industry supervisors were understandably busy involved in clinical research projects to meet client requests. Lockdown measures stalled many investigations, having a domino effect on doctorate projects based there. At the same time, the detachment of industry PhDs from research institutions and universities negatively affected their learning progress. The main scientific activities were mostly virtual and we missed the stimulus of having an audience present, while many such events were inadequately organized and prone to technical glitches. Virtual learning left gaps in milestone competencies like collaboration and the development of a critical approach to research questions and results. However, we are thankful for online platforms. Regardless of the complexity of our position, many of us took advantage of the lockdown by completing online courses and taking part in virtual conferences. Virtual platforms at least allowed us to have some communication and to develop more valuable computational skills than ever before, which were also applied to our projects. WHAT PHD STUDENTS CAN DO DURING GLOBAL EMERGENCIES? Doctorate students aim to find the answers to complex scientific problems and need to excel in critical thinking and correct decision-making, which already imposes pressure on them. Experiencing external pressures through a global pandemic makes it harder to face the challenges associated with research. Here we offer our advice to students that could be experiencing similar global emergencies: Mental wellbeing is one of the biggest challenges one will face when conducting a PhD project in such peculiar times. Even under the best circumstances, one cannot be productive at all times. Therefore, we recommend PhD students to avoid harsh self-criticism if they are lack motivation. We strongly encourage PhD students to share feelings with their peers and colleagues in the same consortium or institution and thus to be open and talk about all problems. We created a group chat where we shared our thoughts and worries. This exercise made us realize that we were not alone and others could relate to our emotions, which was comforting. It is important to rely on other students and researchers to find personal support. Do not hesitate to reach out to your supervisor for help regarding your mental wellbeing as this can have an impact on your work. Good supervision and communication are crucial for the proper development and success of your project. To make the most out of a PhD project we recommend that PhD students take advantage of all opportunities and plan. Design experiments to be performed during times when you can enter the laboratory and plan to generate enough data that you can analyze if a new lockdowns arises. We recommend students to start writing anything related to their research field. For example, write the introduction of the PhD thesis, methodologies that will be used, write a review article, and so on. PhD students will have to write at some point, so they should not hesitate to start even with no results or experience in the field they have just embarked on. Additionally, online seminars can be followed as well as online courses, for example to develop new computational or experimental skills. CONCLUSION Despite all the difficulties, we feel fortunate to be part of the ARCH MSCA ITN program. In December 2021, after 2 years of travel restrictions, we finally met for the first time in person in Rome. Here students and supervisors used this opportunity to begin collaborations, present projects, discuss, and overcome limitations. The COVID-19 pandemic continues to have a significant impact on scientists. PhD students completing their projects throughout the global pandemic have suffered immense isolation and anxiety. Despite recurring delays throughout our project, we feel we have emerged as efficient workers, excellent planners and have developed strong social skills virtually and in person. Those experiencing similar global emergencies should share their experience with peers and colleagues, and find ways to efficiently transit towards effective solutions. Finally, we hope that PhD students experiencing such situations are acknowledged for the time lost and hope that funding agencies recognize that time extensions should be accompanied by financial compensation. DISCLOSURES The authors have no conflicts of interest to disclose. SOURCE OF FUNDING This project has received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement no. 813091 (ARCH, age-related changes in hematopoiesis).

We describe a project-based learning (PBL) program that combines student-driven projects with year-long mentorship to inspire high school students to pursue science, technology, engineering, and math (STEM). Previous studies indicate that PBL improves learning outcomes, teamwork, and long-term interest (1–4). Separate work suggests that long-term mentorship (LTM) programs can promote a pipeline into higher education and STEM for students from underrepresented backgrounds (5, 6).We sought to combine PBL and LTM through a single program called Future Advancers of Science and Technology (FAST). FAST was started at Andrew P. Hill High School (AHHS), a public magnet school in San Jose, CA. Fifty-eight percent of students at AHHS receive free lunches, and 10% receive reduced-price lunches. AHHS academic staff had identified a need for reliable and positive role models in students' lives, especially in STEM fields. FAST aimed to fill that need and help students explore science and engineering through small-group projects.Each FAST program year (Fig 1) begins by working with science teachers from partner schools to identify and recruit students who are “curious, but in need of inspiration.” FAST then matches students with mentors, who are graduate students from a local university. With the guidance of their mentors, students then spend the next 6 months investigating an open question in science or prototyping a solution to an engineering problem. Mentees are encouraged to let their own interests steer the direction of projects, while mentors use their scientific experience and ability to gather information to help develop their mentees' ideas. Projects are conducted in 3 phases of approximately 2 months each: (1) brainstorming and problem definition, (2) performing experiments, and (3) analyzing results and presenting work at local science fairs and a culminating symposium at Stanford University. Over the past 5 years, participation in the FAST program has grown significantly (Table 1), as the program has expanded from AHHS to operate at 3 Bay Area high schools. At AHHS, self-reported participant demographics (Table 2) are generally reflective of the AHHS student body (7).Here, we highlight 3 examples of student–mentor teams that worked on biophysics projects, a significant component of the FAST program. These teams illustrate the dynamics of the student–mentor relationship that FAST was designed to foster. Mentor expertise helps students adapt their projects over the year, but students' personal interests control the project direction. Mentors can also provide scientifically relevant social and cultural capital (“science capital” [8]) that allows students to pursue detailed and rigorous projects. Interviews with student participants suggest that this process of student-driven project development leads to personal growth and encourages the pursuit of higher education in STEM fields, especially in biophysics and related disciplines. With LTM and a modest budget of $100/yr, each FAST student could create a novel, rigorous science or engineering project in a relatively low-resource setting.Initially, AHHS junior and FAST participant TP said she was not “the science or engineering type,” but persisted with the program because she formed strong connections with a few of the mentors. TP was interested in how climate change would affect marine life in local salt lakes, especially by altering physical and chemical properties of the lake water. After 6 wk of brainstorming activities with her mentors, TP proposed a project where she would vary salinity, viscosity, and pH of the water and monitor their effects on the reproduction rate of brine shrimp.The project experienced a setback as TP found she was not able to raise enough brine shrimp to gather meaningful data on reproduction rates. Thus, TP decided to switch from observing reproduction to observing swimming behavior. Her mentor suggested quantitative measurements she could make to aid her analysis. As TP varied salinity and viscosity of the water, she tracked individual shrimp swimming speeds with microscopy videos recorded on her cell phone and free image analysis software (9). TP found that doubling and tripling salt concentrations had no substantial effect on swimming speeds. On the other hand, adding a polymer that increased the viscosity by 5%–10% led to a surprising 50%–75% decrease in swimming speed.In this project, TP and her mentors transformed an unfortunate scientific setback into an insightful science project. TP led the changes and pivoted her project on the basis of her observations, supported by her mentor's knowledge of biophysics, which complemented her parallel classroom learning in chemistry. TP found a community in the FAST program, and she became a FAST student leader the following year. As a leader, in addition to carrying out a second project, she helped to recruit additional students and shape the program curriculum. TP reported that her FAST projects inspired her to study Civil and Environmental Engineering at UCLA.AHHS sophomores CN, NN, and CT had never taken a chemistry or physics class, and they each had varying levels of engagement with their science classes, which ranged from “slightly interested” to “not motivated at all.” Over 10 weeks of iterating through ideas and reading scientific literature with their mentor, a Stanford Biology PhD student, the team refined a research question that affected their everyday lives: how do various types of makeup primers lead to different rates of acne or bacterial growth on the surface of skin?The students classified 6 different makeup primer brands as water-, oil-, or silicone-based and measured how well 2 bacterial species commonly found on the skin grew on nutrient media supplemented with different makeup primers. They quantitatively confirmed that oil-based primers led to higher levels of bacterial growth for both strains than either water- or silicone-based primers. To understand this result, they reasoned that opportunistic bacteria may colonize areas of the skin following an overproduction of oil, which leads to inflammation.All 3 students reported that this project helped them learn important lessons about time management and resilience and increased their motivation in science classes. NN wrote, “FAST has allowed me to gain more confidence in my abilities to present my ideas and it has given me an outlet for my creativity. My ability to express my thoughts in a more meaningful way has markedly improved. I am eager to experiment and ask more questions about the unknown.” The students successfully presented this project at local science fairs, and then were invited to compete at the California Science & Engineering Fair. The next year, NN, CN, and CT all returned to FAST to pursue new research questions. This case study demonstrates how student interest in a real-world problem (side effects of different cosmetics) was built into a rigorous scientific project with mentor guidance.In their second year participating in FAST, AHHS seniors HN, ST, and EP wanted to improve CRISPR gene editing efficiency. They identified that biophysical changes in DNA organization during the cell cycle may affect DNA accessibility and hypothesized that arresting cells in different stages of the cell cycle would alter CRISPR editing efficiency. However, they did not know how they might be able to test this in a high school on a budget.Their mentor identified a Cas9 transgenic yeast strain donated from the San Jose Tech Museum that could be easily screened for Cas9 activity based on the color of the colony. The students treated yeast with cell cycle–inhibiting drugs while inducing Cas9 expression, finding that blocking DNA replication with hydroxyurea or cell division with nocodazole increased CRISPR editing over controls by 98% or 36%, respectively.The students won a Grand Prize at the regional science fair and a trip to the International Science and Engineering Fair (ISEF). The experience of attending ISEF was a “culture shock” for EP, where he met students from all over the world, many of whom had access to considerable resources. Despite the excitement of ISEF, HN recounts that “The biggest prize for us was getting our results and finding out they were meaningful.” All 3 students were awarded college scholarships and expressed that FAST and ISEF inspired them to pursue a STEM-related field.This project demonstrates how mentors with access to science capital (8), such as networks with other scientific institutions, can enable students to fully pursue their ambitions.These 3 specific examples of FAST biophysics projects demonstrate the effectiveness of LTM in fostering curiosity-driven, project-based informal learning. A similar pattern emerges from data at a program-wide scale, with students consistently self-reporting they are more likely to apply to college after participating in FAST, despite the fact that many would be the first in their family to matriculate (Table 2).The examples also highlight key features of the FAST program that may contribute to its success, such as student ownership of project directions. Students have reported that after developing a project through FAST, they have felt more empowered to express themselves scientifically and they have better understood the process of pursuing further scientific training. In contrast, prior work has described a disconnect between STEM content in the classroom and its practical application in the real world (10). FAST students have also reported feeling confident in the science-related skills they developed. This development process is typical of effective PBL, wherein students derive a better understanding of scientific content by engaging directly in problem-solving and critical thinking (11, 12).The case studies presented here demonstrate that successful mentorship involves connecting students to their mentors' science capital (8). This can manifest as guidance—stemming from the mentors' technical experience—that allows students to adapt their project over the course of the year. Additionally, mentors have knowledge of specific resources that allow students to surpass common expectations of high school science project depth and rigor. It is possible that these practices are particularly effective for interdisciplinary subjects like biophysics; in our experience, students are curious about biophysical questions but have not covered enough material in high school to be able to design the experiments independently to test their questions without some guidance from their mentor.FAST mentors are motivated to join the program to support the development of the next generation of scientists and inventors. By joining a graduate student volunteer community, mentors are able to build confidence and develop their mentoring skills. Mentors have also reported growth in their perspectives of the capabilities of underprivileged/underresourced students.Work is ongoing to broaden participation continually in Stanford FAST via inclusive recruitment. Efforts are also ongoing to assess program outcomes quantitatively through evidence-based surveys administered over the course of the academic year. Analysis of these survey data will inform efforts to improve the quality and reproducibility of the program. Former FAST student organization leaders have started a FAST 501(c)(3)–designated charitable organization (fastprogram.org) for supporting the development and dissemination of FAST to broader audiences and new chapters. For educators interested in starting chapters or similar programs, key ingredients will include commitments from enthusiastic science teachers together with demonstrated needs arising from students who have potential science interests but are lacking access to resources or science capital.We acknowledge the work of the FAST leadership team and many mentor volunteers over the past 5 years who have contributed to the program's growth and success. We also acknowledge more than 200 students who have completed the program and provided feedback that informs our understanding of the key elements of the program. CJG, KNL, and AD were supported by the National Science Foundation Graduate Research Fellowship program.Original manuscript development: CJG, KNL, ASK, SKT, AD, TAGL. Case study supporting materials: TP, DL, AAB, HN, EP, ST, NN, CN, CT. Case study interviews: KNL, ASK, AD, CJG. Program supervision: CJG, KNL, ASK, AD, GH, PA. Manuscript editing and organization: CJG, KNL, ASK, SKT, AD, TAGL, PA, ZB.

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